title: Hyperosmotic stress induces a large-scale rewiring of 3D chromatin interactions [Hi-C]

first: John Patrick

last: Flores

address: 104 Manning Dr

institute: UNC Chapel Hill

summary: Cells rapidly adapt to hyperosmotic stress through coordinated molecular responses. To determine how three-dimensional (3D) chromatin structure contributes to this process, we profiled chromatin interactions, architectural protein occupancy, and transcriptional dynamics in human cells exposed to sorbitol-induced hyperosmotic stress. We performed time-resolved Hi-C to measure stress-induced remodeling of chromatin loops and domains, CUT&Tag to quantify CTCF, RAD21, YAP1, and H3K27ac occupancy at loop anchors, and RNA-seq to capture stress-responsive transcriptional programs. These data reveal global loss of pre-existing chromatin contacts and concurrent formation of de novo, transient loops enriched for retained CTCF and cohesin, as well as transcriptional responses that are temporally layered and largely decoupled from loop remodeling. This dataset provides a resource for investigating how nuclear architecture and transcriptional regulation respond to hyperosmotic stress.

overall_design: eGFP-YAP HEK293 cells were serum-starved for 1 hour and then exposed to 200 mM sorbitol to induce hyperosmotic stress. Chromatin organization was profiled by in situ Hi-C at eight time points (0 min, 10 min, 30 min, 1 h, 3 h, 6 h, 12 h, and 24 h) to capture the formation, loss, and recovery of chromatin interactions. To assess the generality of chromatin remodeling, additional Hi-C experiments were performed in HEK293 wild-type and HCT116 cells with and without 1 hour of sorbitol treatment. To probe the requirement for architectural proteins, we also performed Hi-C in HCT116 mAID2-CTCF and mAID2-RAD21 degron cell lines treated with 1 μM 5-Ph-IAA to rapidly and reversibly degrade CTCF or RAD21 prior to sorbitol exposure. Transcriptional responses were measured by stranded RNA-seq across a time course (0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h). To quantify changes in architectural protein occupancy, CUT&Tag for CTCF and RAD21 was performed in untreated and 1-hour sorbitol-treated HEK293 cells.

first: JP

first: Andrea A.

last: Perreault

first: Zack

last: Drum

first: Chenxi

last: Xu

first: Doris

last: Cruz Alonso

first: Gelila

last: Petros

first: Yijia

last: Wu

first: Ivana Y.

last: Quiroga-Barber

first: Isha

last: Sahasrabudhe

first: Justin

last: Demmerle

first: Gang Greg

first: Danfeng

last: Cai

first: Douglas

last: Phanstiel


title: CTCF couples long-range loop extrusion and diffusion to mediate a diverse Igk repertoire [HTGTS-VDJ-Seq]

status: Public on Nov 20 2025

city: East Lansing

first: Yu

last: Zhang

state: MI

address: 567 Wilson Rd, Biomedical and Physical Sciences Building, Rm 5176

department: Microbiology, Genetics and Immunology

country: USA

institute: Michigan State University

summary: Dynamic genome folding is important for V(D)J recombination at the immunoglobulin kappa (Igk) locus, which recombines Jk and Vk gene segments across a 3.2 Mb region in both deletional and inversional orientations. Chromatin loop extrusion and diffusion are considered two key mechanisms underlying Igk folding, but how they coordinate remains unclear. Here we show that CTCF is a key regulator coupling loop extrusion and diffusion during Igk V-J rearrangement, promoting recombination in both orientations across long genomic distances. Mechanistically, the CTCF N-terminus promotes long-range loop extrusion that facilitates distal Vk usage by stabilizing cohesin against WAPL release, and also forms loop barriers enabling chromatin diffusion for inversional Vk joining. In CTCF N-terminal-deficient B cells, defects in inversional Vk joining are not restored by WAPL depletion but are instead largely rescued by a dCas9-blockade targeted to the Vk-Jk intergenic region, mimicking the CTCF barrier. Our findings thus highlight how CTCF coordinates distinct genome-folding mechanisms through its dual roles in cohesin stabilization and extrusion barrier formation to ensure the generation of a diverse Igk repertoire.

overall_design: We performed HTGTS-V(D)J-Seq in v-Abl transformed pro-B cells and the various mutant derivatives to study the molecular basis of CTCF's role in Igk recombination

first: Emma

last: Bush


title: Hyperosmotic stress induces a large-scale rewiring of 3D chromatin interactions [Cut & Tag]

city: Chapel Hill

state: NC

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: eGFP-YAP HEK293 cells were serum-starved for 1 hour and then exposed to 200 mM sorbitol to induce hyperosmotic stress. Chromatin organization was profiled by in situ Hi-C at eight time points (0 min, 10 min, 30 min, 1 h, 3 h, 6 h, 12 h, and 24 h) to capture the formation, loss, and recovery of chromatin interactions. To assess the generality of chromatin remodeling, additional Hi-C experiments were performed in HEK293 wild-type and HCT116 cells with and without 1 hour of sorbitol treatment. Transcriptional responses were measured by stranded RNA-seq across a time course (0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h). To quantiy changes in architectural protein occupancy, CUT&Tag for CTCF and RAD21 was performed in untreated and 1-hour sorbitol-treated HEK293 cells.

last: Wang


title: Lamin A/C-regulated cysteine catabolic flux modulates stem cell fate through epigenome reprogramming

city: Mannheim

first: Gergana

last: Dobreva

state: Baden Württemberg

address: Ludolf-Krehl-Str. 7-11

department: Cardiovascular Genomics and Epigenomics

country: Germany

institute: Medical Faculty Mannheim/University of Heidelberg

type: Expression profiling by high throughput sequencing

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: ScRNAseq analysis of data from patients with T1D and healthy donors

status: Public on Nov 15 2025

city: Prague

first: Veronika

last: Niederlova

address: Videnska 1083

country: Czech Republic

institute: Institute of Molecular Genetics of the Czech Academy of Science

summary: Type 1 diabetes (T1D) arises from loss of immune tolerance to pancreatic β-cells, yet its immunologic drivers remain unclear. We performed single-cell transcriptomic profiling of peripheral T cells from children newly diagnosed with T1D, the same children one year later, and healthy controls. At diagnosis, T1D was marked by broadly reduced effector and cytotoxic programs and increased stemness-related signatures across multiple T cell subsets, alongside impaired regulatory features in both Tregs and TR3-56 cells. Flow cytometry from the same cohort and reanalysis of public datasets confirmed these patterns. Together, these data suggest that T1D involves defective T cell effector differentiation and compromised regulatory control, contributing to immune dysregulation and loss of self-tolerance.

overall_design:
Peripheral blood mononuclear cells (PBMCs) were collected from children newly diagnosed with T1D and from healthy donors. A subset of the same T1D patients was re-sampled one year after diagnosis to assess longitudinal changes. CD4 and CD8 T cells were sorted and subjected to single-cell RNA sequencing using the 10x Genomics Chromium platform (5' v2 chemistry). Libraries were prepared according to the manufacturer’s protocol and sequenced on an Illumina NovaSeq 6000 instrument. Raw sequencing data were processed with Cell Ranger (10x Genomics) for demultiplexing, alignment to the GRCh38 reference genome, and UMI counting. Downstream analyses, including clustering, differential gene expression, and gene set enrichment, were performed using Seurat and custom R scripts. Please see also the associated github: https://github.com/Lab-of-Adaptive-Immunity/dia and Zenodo: https://zenodo.org/records/17280190 .

***************************************************************
Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
***************************************************************

first: Juraj

last: Michalik

first: Ondrej

last: Stepanek


title: Hyperosmotic stress induces a large-scale rewiring of 3D chromatin interactions [RNA-Seq]

first: John Patrick

last: Flores

overall_design: HEK293 eGFP-YAP cells were serum-starved for 1 hour and then exposed to 200 mM sorbitol to induce hyperosmotic stress. Chromatin organization was profiled by in situ Hi-C at eight time points (0 min, 10 min, 30 min, 1 h, 3 h, 6 h, 12 h, and 24 h) to capture the formation, loss, and recovery of chromatin interactions. To assess the generality of chromatin remodeling, additional Hi-C experiments were performed in HEK293 wild-type and HCT116 cells with and without 1 hour of sorbitol treatment. Transcriptional responses were measured by stranded RNA-seq across a time course (0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h). To quantiy changes in architectural protein occupancy, CUT&Tag for CTCF and RAD21 was performed in untreated and 1-hour sorbitol-treated HEK293 cells.

first: JP

first: Andrea A.

last: Perreault

first: Zack

last: Drum


title: Transcriptomic analysis of nanoceria treatment in light-induced retinal degeneration in rat

status: Public on Nov 17 2025

city: Messina

first: Luigi

last: Donato

state: Italy

address: via Consolare Valeria, 1

department: BIOMORF

country: Italy

institute: University of Messina

summary: Retinal neurodegenerative diseases such as Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa cause irreversible vision loss due to the limited regenerative capacity of the mammalian retina. Cerium oxide nanoparticles (nanoceria) are emerging therapeutics against oxidative stress and inflammation, major drivers of photoreceptor degeneration, but their mechanisms remain incompletely understood. We performed retinal transcriptomic analysis in a rat AMD model induced by high-intensity light and treated intravitreally with nanoceria. Six groups were analyzed: control, light damage, vehicle, nanoceria, vehicle + light damage, and nanoceria + light damage. Light damage activated inflammatory and apoptotic programs, with upregulation of cytokines (Tnf, Il6, Il1b, Ccl2) and downregulation of photoreceptor genes (Rho, Pde6a/b, Gnat1). Nanoceria treatment counteracted these effects, suppressing pro-inflammatory mediators, restoring antioxidative genes (Nfe2l2, Gclc, Sod2), and enhancing neuroprotective factors (Bdnf, Cntf, Ngf). Pathway analyses revealed inhibition of TNF/NF-κB/IL-17 signaling and activation of PI3K-Akt, JAK-STAT, and neurotrophin pathways. Unexpectedly, nanoceria also modulated amino acid and insulin metabolism (Ass1, Cps1, Insr, Irs1, Slc2a4) and reactivated transcription factors (Ascl1, Sox2, Notch1) typically silent in adult retina. Our findings highlight nanoceria as a multifunctional therapeutic that mitigates retinal degeneration by coordinating oxidative, inflammatory, and regenerative responses, supporting its translational potential to preserve vision in retinal neurodegenerative disease.

overall_design: Six experimental groups were analyzed: control, light damage, vehicle, nanoceria, vehicle + light damage, and nanoceria + light damage (n = 6–7 animals per group). Retinal RNA-seq was performed on Rattus norvegicus (paired-end 150 bp, Illumina NovaSeq 6000). Differential expression and pathway analyses were conducted to assess the impact of nanoceria treatment.

first: Darin

last: Zerti

first: Ignacio

last: Babiloni-Chust

first: Matthias

last: Carl

first: Carmela

last: Rinaldi

first: Lucia

last: Poggi

first: Rosalia

last: D’Angelo

first: Rita

last: Maccarone


title: Age deceleration and reversal gene patterns in dauer diapause

status: Public on Nov 18 2025

city: Cologne

first: Walter

last: Sandt

address: Joseph-Stelzmann-Str. 26

institute: CECAD

summary: The aging process is characterized by a general decrease in physical functionality and poses the biggest risk factor for a variety of diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders among others. Understanding the naturally evolved mechanisms that could slow aging and rejuvenate an animal could provide important concepts as to how aging could be slowed and functionality restored. The C. elegans dauer state is a robust and long-lived alternative developmental state that upon dauer exit has a normal adult lifespan with fully retained fecundity. In order to understand how dauer longevity and rejuvenation following dauer exit is mediated, we here characterized the gene expression changes during dauer and upon exit. We assessed how biological age, as determined via BiT Age, a transcriptional aging clock, is affected during dauer and upon dauer exit. During the dauer stage, we measured a decelerated increase in age compared to the chronological age and an age reversal following dauer exit. We characterized the underlying gene expression patterns that indicate major metabolic shifts as well as enhanced biomolecular degradation. Our data provide new insights into the underlying mechanisms of naturally occurring age deceleration and rejuvenation.

overall_design: RNA-sequencing of C.elegans for 1, 4, 15 and 30 days in dauer diapuse and 6h and 24h post-exit on each of the 4 days, plus L3 as a reference.

first: Khrystyna

last: Totska

first: João C. V. V.

last: Barata

first: David

last: Meyer

first: Bjoern

last: Schumacher


title: c-JUN Enhances CRISPR Knock-In anti-B7-H3 CAR T-cell Function for Treatment of Small Cell Lung Cancer and thoracic SMARCA4-deficient undifferentiated tumors

status: Public on Nov 13 2025

city: Stanford

first: Yiyun

last: Chen

state: California

address: 265 Campus Dr Room G2105

department: Stanford Cancer Institute

institute: Stanford University

summary: Small Cell Lung Cancer (SCLC), a highly lethal disease, limits T-cell responses by downregulating Major Histocompatibility (MHC) class I molecules. Because chimeric antigen receptor (CAR) T-cells are not MHC-restricted, they may provide a powerful strategy against SCLC. However, few CAR targets for SCLC have been identified. Here we show that B7-H3/CD276 is expressed on the surface of SCLC and thoracic SMARCA4-deficient undifferentiated tumor (UT) cells that can clinicopathologically mimic SCLC. Thoracic SMARCA4-deficient UT, despite high B7-H3 expression, limit killing by B7-H3 CAR-T cells via secretion of transforming growth factor beta 1 (TGFB1). To overcome tumor-driven CAR-T cell suppression, we knocked-in c-JUN alongside a B7-H3 CAR into the TRAC locus of primary human T-cells utilizing CRISPR/Cas9. Non-viral c-JUN+B7-H3 CAR-T cells show enhanced killing of both SCLC cells with low antigen density and thoracic SMARCA4-deficient UT, providing a platform to address these highly aggressive entities. We also provide evidence that GMP clinical scale manufacturing is feasible for c-JUN+B7-H3 CAR-T cells.

overall_design: CAR T cells were derived from the plate-bound stimulation assay described above and collected after ~20 hours of incubation. Cells were counted to ensure a maximum number of 500000 per sample.

first: Hyatt

last: Balke-Want

first: Elena

last: Sotillo

first: Crystal

middle: L

last: Mackall

first: Steven

middle: A

last: Feldman


title: Hepatocyte-specific epidermal growth factor receptor (EGFR) deletion attenuates acetaminophen-induced liver injury in mice [RNA-seq AVITI]

city: Pittsburgh

first: Shuchang

last: Liu

state: PA

address: 203 Lothrop Street

institute: University of Pittsburgh

summary: Epidermal growth factor receptor (EGFR) is mostly known for its proliferative role in liver. Our earlier investigations indicated a paradoxical cell-death promoting facet of EGFR in acetaminophen (APAP)-induced liver injury (AILI) model. The current study investigates this unexpected role of EGFR in promoting AILI using a hepatocyte-specific EGFR deletion mouse model. Hepatocyte-specific EGFR-deficient mice were generated by administering AAV8-TBG-CRE in EGFRfl/fl mice and were subsequently treated with a severely toxic dose (500 mg/kg) of APAP. Liver injury, regeneration and associated signaling pathways were assessed at different time intervals. EGFR deletion significantly attenuated the progression of liver injury (beyond 12hr post-APAP) without altering early liver injury (up to 6 hr) following APAP overdose. Consistently, the key injury initiating events such as APAP-protein adducts formation and early JNK activation remained intact in EGFR-deficient mice. However, EGFR deletion restricted prolonged JNK activation and its mitochondrial translocation, resulting in reduced propagation of mitochondrial damage and release of cell death drivers. Further, the replenishment of antioxidant glutathione (GSH), which is known to limit the progression of liver injury, was strikingly faster in EGFR-deficient mice. RNA-seq analysis and consequent validation revealed marked upregulation of autophagy and its transcriptional regulator TFEB, a key response to remove damaged mitochondria, in EGFR-deficient mice. Paradoxically, EGFR deletion also promoted compensatory liver proliferative response secondary to decreased progression of liver injury. Overall, hepatocyte-specific EGFR deletion halted the progression of AILI. Our study established an unexpected death promoting function of EGFR in AILI progression, which has wide implications in liver biology.

overall_design: Wild-type and hepatocyte-specific EGFR knockout mice were given 500 mg/kg of Acetaminophen (APAP). Liver tissues were harvested at 0, 1, 3, 6, 12, and 24hr post-APAP overdose. Bulk RNA-seq was measured using AVITI sequencer

first: Siddhi

last: Jain

first: Gillian

last: Williams

first: Ranjan

last: Mukherjee

first: Anne

last: Orr

first: Jia-Jun

first: Silvia

first: Joseph

last: Locker

first: Bharat

last: Bhushan


title: Synergistic Inhibition of CHK1 and MUS81 to target replicative stress in high-risk neuroblastoma

city: Ghent

first: Sarah-Lee

last: Bekaert

state: No state

address: Corneel Heymanslaan 10

country: Belgium

institute: UGent

summary: Neuroblastoma (NB) is a pediatric tumor marked by genetic heterogeneity and frequent chromosomal alterations, including MYCN amplification and 17q gain, both linked to poor prognosis. These alterations affect key genes involved in transcriptional regulation and DNA damage response (DDR). NB cells experience high replicative stress (RS), making them particularly sensitive to DDR inhibition. Through integrative bioinformatics, genes such as EME1, RAD51C, and FANCJ on 17q were identified as critical in RS regulation. Targeting the downstream endonuclease MUS81, especially in combination with CHK1 inhibition, produced synergistic anti-tumor effects. This combination offers a promising strategy to exploit RS vulnerability in high-risk NB.

overall_design: RNA-sequencing of high dose Dyngo4a and combination drugging of Dyngo4a and prexasertib in IMR-32 neuroblastoma cell lines.

first: Elien

last: Hilgert

first: Fien

last: Martens

first: Suzanne

last: Vanhauwaert

first: Christophe

last: Vanneste

first: Frank

last: Speleman

first: Lisa

last: Depestel

first: Kaat

last: Durinck


title: Methylome dataset by Whole-genome bisulfite sequencing (WGBS) using whole blood of dogs

status: Public on Nov 14 2025

city: Fujimino

first: Miyuki

last: Nakamura

state: Saitama

country: Japan

institute: KDDI research Inc

type: Methylation profiling by high throughput sequencing


title: CHN1 as a Predictive Biomarker for Atopic Dermatitis-related Depression

city: Wuhan

first: Yifei

last: Wang

address: Baofeng street

country: China

institute: Huazhong University of Science and Technology

summary: The comorbidity of Atopic Dermatitis (AD) and depression has garnered increasing attention in recent years. Yet, the immunopathological mechanisms underlying this connection remain unclear. To bridge this gap, we collected peripheral blood mononuclear cell samples from 20 AD patients with and without depression, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the immune regulatory networks and identify key genetic markers for the depression comorbidity in AD patients. Our analysis revealed 394 differentially expressed genes in AD patients with depression as compared to those non-depression counterparts. Weighted gene co-expression network analysis pinpointed a pink module encompassing 83 genes strongly linked to depression. Functional enrichment analysis of critical module genes revealed significant enrichment scores in neurotransmitter uptake and the negative regulation of T-helper (Th) 17 cell differentiation. Furthermore, machine learning models of least absolute shrinkage and selection operator and support vector machines highlighted CHN1 as a potential pivotal gene upregulated in AD patients with depression. The expression level of CHN1 demonstrated positive correlation with Th2 and Th17 cytokine families, as well as with the Hospital Anxiety and Depression Scale-Depression score and Eczema Area and Severity Index. Validation experiments on clinical samples of an additional 20 participants confirmed the significant upregulation of CHN1 in depressed AD patients. This study is the first to unveil the intricate inflammatory and immune pathways underlying AD-associated depression, shedding light on the critical role of CHN1 connecting inflammation and neuropsychiatric symptoms.

overall_design: We collected peripheral blood mononuclear cell samples from 20 AD patients with (DAD) and without depression (NAD), and performed RNA sequencing analysis.


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [mouse_Tconv_ChIP-seq]

city: San Francisco

first: Alexander

last: Marson

state: CA

address: 1650 Owens St.

institute: UCSF Gladstone Institutes

summary: FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Tregs and Tconvs to discover cis-regulatory elements (CREs) and trans-regulators of FOXP3. Tconv FOXP3 expression depended on a subset of Treg CREs and Tconv-selective positive (NS+) and negative (NS-) CREs. Combinatorial silencing of Tconv CREs revealed their epistatic logic. The CREs are occupied and regulated by TFs we identified as critical regulators of FOXP3. Finally, mutagenesis of murine NS- revealed that it is critical for restriction of FOXP3 expression to Tregs. We discover CRE and TF circuitry controlling FOXP3 expression and reveal cell and species-specific regulation of a gene indispensable to immune homeostasis.

overall_design: ChIP-seq in mouse T cells. ChIP-seq was conducted in using DSG/formaldehyde fixation.

first: Jennifer

middle: M

last: Umhoefer

first: Maya

last: Arce

first: Sivakanthan

last: Kasinathan

first: Sean

last: Whalen

first: Rama

last: Dajani

first: Sanjana

last: Subramanya

first: Laine

last: Goudy

first: Julia

last: Belk

first: Royce

last: Zhou

first: Minh

middle: T

last: N Pham

first: Wenxi

last: Zhang

first: Rosmely

last: Hernandez

first: Carinna

last: Tran

first: Nikhita

last: Kirthivasan

first: Jacob

middle: W

last: Freimer

first: Cody

last: Mowery

first: Vinh

last: Nguyen

first: Mineto

last: Ota

first: Benjamin

middle: G

last: Gowen

first: Dimitre

middle: R

last: Simeonov

first: Gemma

last: Curie

first: Zhongmei

last: Li

first: Andy

middle: Y

last: Chen

middle: E

last: Corn

first: Howard

last: Chang

first: Qizhi

last: Tang

first: Luke

last: Gilbert

first: Ansuman

last: Satpathy

first: Katherine

middle: S

last: Pollard


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [human_Tconv_ChIP-seq]

first: Alexander

last: Marson

overall_design: ChIP-seq in human T cells. ChIP-seq was conducted in using DSG/formaldehyde fixation.

first: Jennifer

last: Umhoefer

first: Maya

last: Arce

first: Sivakanthan

last: Kasinathan

first: Sean

last: Whalen

first: Rama

last: Dajani

first: Sanjana

last: Subramanya

first: Laine

last: Goudy

first: Julia

last: Belk

first: Royce

last: Zhou

first: Minh

last: N Pham

first: Wenxi

last: Zhang

first: Rosmely

last: Hernandez

last: Tran


title: Single cell resolution of an open chromatin signature in persister tumor cells

city: Rochester

first: Alexandre

last: Gaspar-Maia

state: MN

address: 200 First street SW

institute: Mayo Clinic

summary: To characterize transcriptional and chromatin accessibility changes that promote survival of residual cancer following chemotherapy, we performed single-cell multiomic profiling (snRNA+snATAC) on a cohort of non-malignant fallopian tube, treatment-naive, and neoadjuvant chemotherapy (NACT)-treated high-grade serous ovarian cancer (HGSOC) samples. From this analysis, we identified an epigenetic signature that precedes expression and defines the drug-tolerant persister state.

overall_design: Nuclei from ovarian cancer tissue were isolated and processed for single cell Multiome sequencing following 10x Genomics protocol.

first: Mihai

last: Dumbrava

first: Wazim

last: Mohammed Ismail

first: Leticia

last: Sandoval

first: Amelia

last: Mazzone

first: Xiaonan

last: Hou

first: Shariska

last: Harrington

first: Scott

middle: H

last: Kauffmann

first: S

middle: J

last: Weroha


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRoff_RNA-seq]

first: Alexander

last: Marson

overall_design: Total RNA-seq in CRISPRoff-edited human Tconvs from 2 donors. CRISPRoff gRNAs target NS- or the AAVS1 control region (x2).

first: Jennifer

last: Umhoefer

first: Maya

last: Arce

first: Sivakanthan

last: Kasinathan

first: Sean

last: Whalen

first: Rama

last: Dajani

last: Subramanya

first: Carinna

first: Nikhita

last: Kirthivasan

first: Jacob

last: Freimer

first: Cody

last: Mowery

first: Vinh

last: Nguyen

first: Mineto

last: Ota

first: Benjamin

last: Gowen

first: Dimitre

last: Simeonov

first: Gemma

last: Curie

first: Zhongmei

last: Li

first: Andy

last: Chen

last: Corn

first: Howard

last: Chang

first: Qizhi

last: Tang

first: Luke

last: Gilbert

first: Ansuman

last: Satpathy

first: Katherine

last: Pollard


title: Hepatocyte-specific epidermal growth factor receptor (EGFR) deletion attenuates acetaminophen-induced liver injury in mice [RNA-seq Illumina]

first: Shuchang

last: Liu

overall_design: Wild-type and hepatocyte-specific EGFR knockout mice were given 500 mg/kg of Acetaminophen (APAP). Liver tissues were harvested at 0, 1, 3, 6, 12, and 24hr post-APAP overdose. Bulk RNA-seq was measured using Illumina sequencer.

first: Siddhi

last: Jain

first: Gillian

last: Williams

first: Ranjan

last: Mukherjee

first: Anne

last: Orr

first: Jia-Jun

first: Silvia

first: Joseph

last: Locker

first: Bharat

last: Bhushan


title: Loss of function of chromatin remodeler OsCLSY4 led to RdDM-mediated mis-expression of endosperm-specific genes effecting grain qualities [CLSY4_small_RNA_sequencing]

city: Bangalore

first: Shivaprasad

last: Padubidri V.

address: UAS-GKVK Campus

country: India

institute: National Centre for Biological Sciences - TIFR

type: Non-coding RNA profiling by high throughput sequencing

summary: Knock down of CLSY4 in rice caused endosperm development defects. We investigated the molecular effects of loss of CLSY4 in rice  endosperm by profiling sRNA, targeted bisulfite PCR,whole genome bisulfite sequencing and mRNA transcriptomes .These analyses revealed the  roles of CLSY4 in Endosperm

overall_design: We have performed small RNA sequencing to understand the small RNA status of endosperm upon CLSY4 knockdown

first: Padubidri

middle: V

last: Shivaprasad

first: Pal

last: Avik Kumar


title: Loss of function of chromatin remodeler OsCLSY4 led to RdDM-mediated mis-expression of endosperm-specific genes effecting grain qualities [Bisulfite_sequencing]

summary: Knock down of CLSY4 in rice caused endosperm development defects. We investigated the molecular effects of loss of CLSY4 in rice  endosperm by profiling sRNA, targeted bisulfite PCR,whole genome bisulfite sequencing and mRNA transcriptomes. These analyses revealed the roles of CLSY4 in Endosperm.

overall_design: We have performed whole genome bisulfite sequencing to understand the methylation status of endosperm upon CLSY4 knockdown


title: Loss of function of chromatin remodeler OsCLSY4 led to RdDM-mediated mis-expression of endosperm-specific genes effecting grain qualities [RNA-Seq]

summary: Knock down of CLSY4 in rice caused endosperm development defects. We investigated the molecular effects of loss of CLSY4 in rice  endosperm by profiling sRNA, targeted bisulfite PCR,whole genome bisulfite sequencing and mRNA transcriptomes .These analyses revealed the roles of CLSY4 in Endosperm

overall_design: We have performed RNA sequencing to understand transcriptomic status of endosperm upon CLSY4 knockdown


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRi]

first: Alexander

last: Marson

summary: FOXP3 is a lineage-defining transcription factor (TF) for immune-suppressive regulatory T cells (Tregs). While mice exclusively express FOXP3 in Tregs, humans also transiently express FOXP3 in stimulated conventional CD4+ T cells (Tconvs). Mechanisms governing these distinct expression patterns remain unknown. Here, we performed CRISPR screens tiling the FOXP3 locus and targeting TFs in human Tregs and Tconvs to discover cis-regulatory elements (CREs) and trans-regulators of FOXP3. Tconv FOXP3 expression depended on a subset of Treg CREs and Tconv-selective positive (TcNS+) and negative (TcNS-) CREs. Combinatorial silencing of Tconv CREs revealed their epistatic logic. The CREs are occupied and regulated by TFs we identified as critical regulators of FOXP3. Finally, mutagenesis of murine TcNS- revealed that it is critical for restriction of FOXP3 expression to Tregs. We discover CRE and TF circuitry controlling FOXP3 expression and reveal evolution of mechanisms regulating a gene indispensable to immune homeostasis.

overall_design: Pooled CRISPR screens in human regulatory T cells (Tregs) and conventional T cells (Tconvs). The CRISPRi locus tiling library targets the FOXP3 locus. Tconv screens were conducted in 2 donors. Treg screens were conducted in 2 donors.

first: Jennifer

last: Umhoefer

first: Maya

last: Arce

first: Sivakanthan

last: Kasinathan

first: Sean

last: Whalen

first: Rama

last: Dajani

first: Sanjana

last: Subramanya

first: Laine

last: Goudy

first: Julia

last: Belk

first: Royce

last: Zhou

first: Minh

last: N Pham

first: Wenxi

last: Zhang

first: Rosmely

last: Hernandez

first: Carinna

last: Tran

first: Nikhita

last: Kirthivasan

first: Jacob

last: Freimer

first: Cody

last: Mowery

first: Vinh

last: Nguyen

first: Mineto

last: Ota

first: Benjamin

last: Gowen

first: Dimitre

last: Simeonov

first: Gemma

last: Curie

first: Zhongmei

last: Li

first: Andy

last: Chen

first: Howard


title: Loss of function of chromatin remodeler OsCLSY4 led to RdDM-mediated mis-expression of endosperm-specific genes effecting grain qualities

first: Shivaprasad

last: Padubidri V.

overall_design: Refer to individual Series


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [human_Treg_ChIP-seq]

first: Alexander

last: Marson

first: Jennifer

last: Umhoefer

first: Maya

last: Arce

first: Sivakanthan

last: Kasinathan

first: Sean

last: Whalen

first: Rama

last: Dajani

first: Sanjana

last: Subramanya

first: Laine

last: Goudy

first: Julia

last: Belk

first: Royce

last: Corn

last: Chang

first: Qizhi

last: Tang

first: Luke

last: Gilbert

first: Ansuman

last: Satpathy

first: Katherine

last: Pollard


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry [CRISPRKO]

overall_design: Pooled CRISPR screens in human regulatory T cells (Tregs) and conventional T cells (Tconvs). The CRISPR KO TF library targets transcription factors and select chromatin modifiers and immune genes of interest. Tconv screens were conducted in 3 donors. Treg screens were conducted in 2 donors.

last: Zhou

first: Minh

last: N Pham

first: Wenxi

last: Zhang

first: Rosmely

last: Hernandez

first: Carinna

last: Tran

first: Nikhita

last: Kirthivasan

first: Jacob

last: Freimer

first: Cody

last: Mowery

first: Vinh

last: Nguyen

first: Mineto

last: Ota

first: Benjamin

last: Gowen

first: Dimitre

last: Simeonov

first: Gemma

last: Curie

first: Zhongmei

last: Li

first: Andy

last: Chen


title: MSS2-mediated ROS and calcium are essential for Candida albicans invasive behavior and virulence

status: Public on Nov 12 2025

city: Taipei

first: Ching-Hsuan

last: Lin

state: Taiwan

address: National Taiwan University, 1 Roosevelt Rd. Sec. 4

department: Department of Biochemical Science and Technology

country: Taiwan

institute: National Taiwan University

summary: Mitochondrial function is essential for virulence in Candida albicans, yet the mechanism by which mitochondria influence invasive behavior remains largely undefined. Here, we uncover a novel, mitochondria-centered mechanism in which the mitochondrial-associated gene MSS2 controls invasive growth through the regulation of calcium–ROS homeostasis. Deletion of MSS2 exhibits impaired invasive growth on solid agar without affecting hyphal formation in liquid, suggesting a unique contact-specific regulatory program. Indeed, we found that the regulation of these processes by Mss2 is linked to the regulation of cytosolic calcium levels and cellular ROS production. Furthermore, transcriptomic profiling identified the MSS2-regulated genes, UME6, SAC1, RIM8, and ORF19.1841, whose expression is dependent on calcium and ROS levels. Restoration of invasive phenotypes through exogenous ROS confirms the functional significance of this calcium-ROS circuit. In systemic infection models., mutants lacking MSS2 or its downstream genes exhibit severe host cell invasion and virulence defects. Together, this work is the first to reveal that mitochondrial regulation of a coordinated calcium-ROS circuit is indispensable for invasive hyphal growth in C. albicans. These findings further refine the current model of fungal invasive progression and may provide useful information for future studies aiming to target mitochondrial signaling in pathogenic fungi.

overall_design: Total mRNA extracted from wild-type (WT) and mss2Δ strains in RPMI 1640 liquid medium or on RPMI 1640 agar plate for 24 hours at 30°C was analyzed using RNA sequencing.

first: Cai-Ling

last: Ke

first: Hsaio-Yen

last: Tsai

first: Ajinkya

last: Kulkarni

first: Richard

last: Bennett


title: Integrative Single-Cell Analysis of Gene Expression and Chromatin Accessibility Reveals CTCF as a Key Regulator of Stem Cell Differentiation and Lung Morphogenesis [scRNA-seq]

city: shenzhen

first: Jiang

last: Yamei

address: longfei

institute: The Chinese University of Hong Kong-Shenzhen

summary: The lungs develop into an intricate tree-like structure through proximal-distal patterning and branching morphogenesis. However, the gene regulatory programs that dictate embryonic lung development remain largely unclear. Here, we profile gene expression and chromatin accessibility in mouse embryonic lungs to generate a multi-omics atlas at single-cell resolution. By integrative analyses, we dissect 10 cell type-specific gene expression signatures and characterize177,990 cis-regulatory elements (CREs), 36,114 differential accessible chromatin regions (DARs), 27,628 gene-to-peak linkages, 632 highly regulated genes (HRGs), and their binding transcription factors (TFs). We also explore candidate regulators driving lung progenitor developmental trajectory and discover the important role of the AP-1 complex in mesenchymal differentiation. Based on this multi-modal dataset, we delineate gene regulatory networks (GRNs) across various cell types. Finally, using the Ctcf conditional knockout mouse model combined with multiple approaches, we reveal CTCF as a crucial regulator of Sox2+ progenitor specification and lung branching morphogenesis by reprogramming transcriptome and chromatin accessibility. Therefore, this study provides multi-omics resources and mechanistic insights for transcription regulation of lung morphogenesis.

overall_design: To comprehensively study the heterogeneity and regulatory mechanisms of lung morphogenesis, we performed scRNA-seq profiling of nuclei extracted from embryonic day 12.5 (E12.5) lungs.

first: Yamei

last: Jiang

first: Fujing

last: Huang

first: Wei

last: Wei

first: Mathias

last: Hochgerner

first: Kaijun

first: Xinna

last: Zhang

first: Hua

last: He

first: Miao

last: Yu

first: Xinhua

first: Xiaofang

last: Tang

first: Shenfei

last: Sun


title: Integrative Single-Cell Analysis of Gene Expression and Chromatin Accessibility Reveals CTCF as a Key Regulator of Stem Cell Differentiation and Lung Morphogenesis [multi-omics]

overall_design: To comprehensively study the heterogeneity and regulatory mechanisms of lung morphogenesis, we performed multi-omics profiling of nuclei extracted from embryonic day 12.5 (E12.5) lungs using 10x Genomics paired snRNA-seq and snATAC-seq techniques.


title: Loss of function of chromatin remodeler OsCLSY4 led to RdDM-mediated mis-expression of endosperm-specific genes effecting grain qualities [CLSY4_bisulfite_PCR]

first: Shivaprasad

last: Padubidri V.

overall_design: We have performed targeted bisulfite sequencing to understand the methylation status of leaf upon CLSY4 and CLSY3 knockdown

first: Padubidri

last: Shivaprasad

first: Pal

last: Avik Kumar


title: An FXR-Casp6 axis-mediated bile acid/gut microbiota sensing modulates neonatal β-cell mass expansion [scRNA-Seq]

city: Shanghai

first: Chenyang

last: Fu

address: 197 Ruijin Road II

department: Department of Endocrine and Metabolic Diseases

institute: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

summary: Weaning diet switch brings gut microbiome maturation along with postnatal formation of sufficient matured β-cell mass. The matured gut microbiota elevated agonistic components of bile acid (BA) pool towards farnesoid X receptor (FXR) that was paralleling with the declined β-cell FXR expression. To investigate whether BA/FXR could link postnatal β-cell development and gut microbiota maturation, we forced persistent FXR expression in β cells (βFxrKI) and found decreased neonatal β-cell mass growth and increased glycemia in weaned βFxrKI mice, which could be partially recovered by ablating gut microbiota before weaning. scRNA and scATAC seq analysis showed different β cell growth trajectories with suppressed intrinsic cell proliferation and elevated cell apoptosis in βFxrKI. Caspase-6 was then identified as a dominant β-cell FXR downstream effector to mediate its regulation. The negative regulation of the FXR-Casp6 axis on postnatal β-cell mass expansion reflected a programmed cellular response to gut microbiota maturation in neonatal mice.

overall_design: We constructed a mouse model of β-cell-specific FXR overexpression (βFxrKI). The overall goal of this study was to define the transcriptome alterations for pancreatic islet cells in control and βFxrKI mice from postnatal 1 week to 3 weeks, and we further identified dominant FXR targets in β cells. For the construction of  βFxrKI mice, a cassette of Fxr (Nr1h4) cDNA sequence with a 3xflag in N terminal followed a sequence containing the CAG promoter and loxp-PGK-Neo-polyA-loxp and was knocked in the first intron of the Rosa26 site. Fragment of loxp-PGK-Neo-polyA-loxp prevents the transcription of Nr1h4 cDNA as a “STOP” sequence. When mice with this knock-in fragment were mating with Ins2-Cre mice, the floxed sequence was cut off, Nr1h4 can be driven to express, and the mice with specifically forced Fxr expression in β cells were generated.

first: Yanyun

last: Gu


title: An FXR-Casp6 axis-mediated bile acid/gut microbiota sensing modulates neonatal β-cell mass expansion [scATAC-Seq]


title: Expression data from pre-cancerous pancreatic tissue from a murine model of pancreatic ductal adenocarcinoma (PDAC) and control pancreas

city: Marseille

first: Ghislain

last: BIDAUT

address: 27 Bd Leï Roure

department: Bioinformatics

country: France

institute: Centre de Recherche en Cancérologie de Marseille

summary:
We used microarrays to detail the global gene expression signature of PDAC and to identify distinct up- and down-regulated transcripts in pre-cancerous pancreatic tissue compared to control pancreas.
We also established from this dataset the metabolic signature of pre-cancerous pancreas to define new metabolic therapeutic targets for PDAC.

overall_design: Pre-cancerous tissue wase removed at an early stage of transformation in 4-week-old mice with Mixed genetic background : B6CBAF1 x C57BL/6 x 129/Sv x FVB/n.

first: S

last: Vasseur

first: F

last: Guillaumond

first: G

last: Bidaut

last: Efthymiou


title: Developmental convergence and divergence in human stem cell models of autism spectrum disorder

city: Santa Monica

first: Lucy

middle: K

last: Bicks

address: 1033 3rd street, apartment 106, apartment 106

department: Neurology

institute: UCLA School of Medicine

summary: Two decades of genetic studies in autism spectrum disorder (ASD) have identified over a hundred genes harboring rare risk mutations. Despite this substantial heterogeneity, transcriptomic and epigenetic analyses have identified convergent patterns of dysregulation across ASD post-mortem brain. To identify shared and distinct mechanisms of ASD-linked mutations, we assembled the largest patient hiPS cell cohort to date, consisting of 70 hiPS cell lines after stringent quality control representing 8 ASD-associated mutations, idiopathic ASD, and 20 lines from non-affected controls. We used these hiPS lines to generate human cortical organoids (hCO), profiling by RNAseq at four distinct timepoints up to 100 days after in vitro differentiation. Early timepoints harbored the largest mutation-specific changes, but different mutations converged on shared transcriptional changes as development progressed. We identified a shared RNA and protein interaction network, which was enriched in ASD risk genes and predicted to drive the observed down-stream changes in gene expression. CRISPR-Cas9 screening of these candidate transcriptional regulators in induced human neural progenitors validated their downstream molecular convergent effects. These data illustrate how genetic risk can propagate via transcriptional regulation to impact convergently dysregulated pathways, providing new insight into the convergent impact of ASD genetic risk on human neurodevelopment.

overall_design:
To investigate the effects of ASD-linked mutations on gene expression changes across development in human cortical organoids.

***************************************************************
Submitter states that missing raw data are being made available for controlled access in dbGaP.
***************************************************************

first: Aaron

last: Gordon

first: Se-Jin

last: Yoon

first: Sergiu

middle: P

last: Pasca

first: Daniel

last: Geschwind


title: FOXP3 Expression Depends on Cell-Type Specific Cis-Regulatory Element and Transcription Factor Circuitry

first: Alexander

last: Marson

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damage.

summary: The excessive production of extracellular matrix (ECM) and the metabolic adaptations in pancreatic ductal adenocarcinoma (PDAC) contribute individually to enhanced chemoresistance, dramatic tumor progression and dismal patient survival. However, the ECM-driven metabolic alterations that promote chemoresistance in PDAC are less well described. Here, we use in-vitro-generated ECM bio-scaffolds that recapitulate cell-ECM interactions and induce broad metabolic alterations in PDAC cells. High-throughput integration of multi-omics datasets coupled with metabolic tracing showed that the ECM favors the accumulation of guanylates in PDAC cells and alleviation of oxaliplatin-induced DNA damage, thus supporting PDAC cell proliferation. This is controlled by the GMP-producing enzyme IMPDH, the expression of which was upregulated in resected PDAC tissue from patients who displayed low survival. We propose that targeting ECM-modulated metabolic processes in PDAC may be a more effective and safer approach, without the negative side effects of direct targeting of the ECM itself.

overall_design: RNAseq profiling of tumor cells isolated from a pancreatic ductal adenocarcinoma murine model when cultivated on the extracellular matrix of patient-derived cancer-associated fibroblasts compared to when grown on matrix-free tissue culture vessels.

first: Georgios

first: Eugénie

last: Lohmann

first: Sophie


title: Polyamine-dependent metabolic shielding regulates alternative splicing

status: Public on Nov 11 2025

city: Derio

first: Arkaitz

last: Carracedo

address: Bizkaia Science and Technology Park, building 801A

country: Spain

institute: CIC bioGUNE

summary: Metabolites are central to cellular homeostasis. Whereas much emphasis has been placed on their relevance to meet energetic and biosynthetic demands, metabolic intermediates also function as signaling molecules. Here we show that polyamines, small polycations critical to cellular homeostasis1-3, regulate the process of alternative pre-mRNA splicing. We find that the inhibition of polyamine synthesis increases the phosphorylation of spliceosomal proteins, concomitant with a remarkable perturbation of alternative splicing in cells and tissues. Mechanistically, molecular modeling combined with biochemical assays revealed that polyamines bind to acidic phosphorylatable motifs in splicing factors of the U2 snRNP SF3 subcomplex, thus preventing the action of kinases. The molecular process through which polyamines regulate protein phosphorylation is a phenomenon that we define as “metabolic shielding”.

overall_design:
Deep-coverage RNA-seq analysis to test the effect of polyamine biosynthesis inhibition on splicing in DU145 cells.
Deep-coverage RNA-seq analysis to test the effect of polyamine biosynthesis inhibition on splicing upon the absence or presence of U2 snRNP SF3A3 subcomplex member.
Deep-coverage RNA-seq analysis to test the effect of polyamine biosynthesis inhibition on splicing in the skeletal muscle of wild-type mice.
Deep-coverage RNA-seq analysis to test the effect of polyamine biosynthesis inhibition on splicing in HeLa cells.
Deep-coverage RNA-seq analysis to test the effect of polyamine biosynthesis inhibition on splicing in mouse embryonic stem cells under the effect of SAM486A and DFMO
Deep-coverage RNA-seq analysis to test the effect of polyamine biosynthesis inhibition on splicing in mouse embryonic stem cells under the effect of SAM486A, DFMO and BENSpm

first: Amaia

last: Zabala-Letona

first: Mikel

last: Pujana-Vaquerizo

first: Belen

last: Martinez-Laosa

first: Maria

last: Ponce-Rodriguez

first: Saioa

last: Garcia-Longarte

first: Isabel

last: Mendizabal

first: Ana

last: Gimeno

first: Malgorzata

last: Rogalska

first: Joycelyn

last: Tan

first: Diana

last: Cabrera

first: Sebastiaan

last: van Liempd

first: Pilar

last: Ximenez-Embun

first: Sergio

last: Espinosa

first: Maider

last: Fagoaga-Eugui

first: Francesca

last: Peccati

first: Ianire

last: Astobiza

last: Arana-Castañares

first: Sarah

last: Cherkaoui

last: Sendino

first: Inés

last: Martín-Barros

last: Ercilla

first: Laura

last: Bozal

first: Onintza

last: Carlevaris

last: Arruabarrena-Aristorena

first: Encarnación

last: Pérez-Andrés

first: Telmo

last: Santamaría-Zamorano

first: Juan

last: Ferrer-Bonsoms

first: Fernando

last: Carazo

first: Maciej

last: Cieśla

first: Cesar

last: Lobato

first: Joan

last: Seoane

first: Natalia

last: Martín-Martín

first: Rosa

last: Barrio

first: James

middle: D

last: Sutherland

last: Aransay

first: Juan Manuel

last: Falcón-Pérez

first: Barbara

last: Martínez-Pastor

first: Angel

last: Rubio

first: Francisco

last: Blanco

first: Michael

last: Hogarty

first: Raphael

last: Morscher

first: Edurne

last: Berra

first: Remigiusz


title: Integrating whole-exome sequencing and scRNA-seq reveal the characteristic in one clear cell renal cell carcinoma sample arising in the setting of VHL disease

city: Nanning

first: Zhenyuan

last: Yu

state: Guangxi

address: Shuangyong road 22

department: Center for Genomic and Personalized Medicine

institute: Guangxi Medical University

summary: Clear cell renal cell carcinoma (ccRCC) arising in the setting of von Hippel–Lindau (VHL) disease is a rare type of kidney cancer and features VHL germline mutation. This type of ccRCC is rarely characterised at the single-cell level. In this work, whole-exome sequencing and single-cell RNA sequencing (scRNA-seq) were conducted on one ccRCC sample with VHL disease. Integrating scRNA-seq and whole-exome sequencing data by the Seurat package, we determined the relationship between single-cell transcriptome features and gene mutations. Immunohistochemistry and immunofluorescence were performed on one VHL germline mutation ccRCC and six non-VHL germline mutation ccRCC samples. We revealed the gene expression characteristics of ccRCC with VHL germline mutation. The frameshift mutations in OBP2A and BCR1, and the elevated expression of COX7A1 were most specific characteristics of ccRCC tumor cells with VHL mutation. And the extensive infiltration of exhausted T cells was the characteristic of tumor microenvironment. In addition, we discovered the relationship between genetic mutations and immune checkpoints. This work highlights the single-cell transcriptome and DNA-level information of this rare ccRCC and will provide more genetic insights and references into this rare disease.

overall_design: ccRCC arising in the setting of VHL disease was used for single-cell RNA sequencing by 10X Genomics.

first: Wenhao

last: Lu

first: Tingwei

last: Jin

first: Xiaoxiang

first: Yixuan

last: Liu

first: Shengzhu

last: Huang

first: Zheng

last: Wen

first: Cheng

last: Su

first: Yu

last: Ye

first: Ziyan

first: Zengnan

last: Mo


title: CDK4/6 and SHP2 mediate BRAF/MEK inhibitor resistance in Class 2 and 3 BRAF mutant cancers

city: Montreal

first: April

last: Rose

address: 3755 chem. de la côte ste Catherine

department: Lady Davis Institute

country: Canada

institute: McGill University

summary: Class 2 and 3 non-V600E BRAF mutations are oncogenic drivers in many cancer types.  Currently, there are no established targeted therapies with proven efficacy for cancers with non-V600E BRAF mutations. We developed the investigator-initiated, Phase II BEAVER clinical trial (NCT03839342) to evaluate the efficacy of BRAF and MEK inhibitors in patients with non-V600E BRAF mutations. The best objective response rate was 14% (3/21). By analyzing genomic data from patient tumors, circulating tumor DNA (ctDNA), patient-derived xenograft (PDX) models generated from enrolled patients, and Class 2 & 3 BRAF mutant cell lines, we discovered MAPK-dependent and independent mechanisms of resistance to BRAF/MEK inhibition. These mechanisms included the acquisition of new mutations in NRAS, MAP2K1, RAF1, and RB in ctDNA at the time of disease progression. CDK4/6 and SHP2 were identified as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors were more effective than BRAF/MEK inhibitors alone in these cancers. https://doi.org/10.1038/s41467-025-68076-7

overall_design: RNA-seq profiling of PDX tumours at experimental endpoint treated with either Vehicle, Binimetinib+Encorafenib, Palbociclib, TNO155, Binimetinib+Encorafenib+Palbociclib, or Binimetinib+Encorafenib+TNO155. RNA-seq profiling of Non-V600 BRAF mutant cancer cell lines treated with DMSO or Binimetinib+Encorafenib for 24 hours.

first: Jennifer

last: Maxwell

first: Emmanuelle

last: Rousselle

first: Chantel

last: Mukonoweshuro

first: Islam

last: Elkholi

first: Melody

last: Riaud

first: Marco

last: Biondini

first: Erica

last: Cianfarano

first: Isabel

last: Soria-Bretones

first: Chantal

last: Tobin

first: Meghan

last: McGuire

first: Ian

last: King

first: Tong

last: Zhang

first: Trevor

last: Pugh

first: Zaid

last: Kamil

first: Marcus

last: Butler

first: Frances

last: Shepherd

first: Natasha

last: Leighl

first: Albiruni

last: Razak

first: Aaron

last: Hansen

first: Sam

last: Saibil

first: Philippe

last: Bedard

first: Peter

last: Siegel

first: Lillian

last: Siu

first: David

last: Cescon

first: Anna

last: Spreafico


title: Filovirus Infection Disrupts Epithelial Barrier Function and Ion Transport in Human iPSC-Derived Gut Organoids

status: Public on Nov 10 2025

city: Boston

first: Pushpinder

last: Bawa

state: Massachusetts

address: 670 Albany St

department: Boston University Medical Campus

institute: Center for Regenerative Medicine

summary: Gastrointestinal (GI) dysfunction, characterized by severe diarrhea and dehydration, is a central contributor to morbidity and mortality in filovirus disease in patients, yet the role of the epithelium in this clinical outcome remains poorly defined. Here, we employ induced pluripotent stem cell (iPSC)-derived human intestinal (HIOs) and colonic organoids (HCOs) to model Ebola virus (EBOV) and Marburg virus (MARV) infection. These organoids are permissive to filovirus infection and support viral replication. Bulk RNA sequencing revealed distinct intestinal and colonic epithelial responses, including apical and junctional disruption and a delayed virus-specific induction of interferon-stimulated genes. Moreover, infection impaired adenylate cyclase signaling and CFTR-mediated ion transport, providing mechanistic insight into virus- induced secretory diarrhea. This platform recapitulates key features of human GI pathology in filoviral disease and serves as a powerful system to dissect host-pathogen interactions and identify therapeutic targets.

overall_design: To assess the effects of filovirus infection on the human gastrointestinal tract, we exposed induced pluripotent stem cell (iPSC)-derived human intestinal organoids (HIOs) and colonic organoids (HCOs) to Ebola virus (EBOV) and Marburg (MARV) virus. Bulk RNA sequencing (bulk RNA-seq) was performed on proximal HIOs (n = 3), distal HIOs (n = 3), and mock-infected controls (n = 3) at 3 days post-infection to identify transcriptomic changes. These findings were further supported by immunohistochemistry and immunofluorescence assays to validate viral infection.

first: Elizabeth Yvonne

last: Flores


title: Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells

status: Public on Nov 07 2025

city: Dallas

first: Samuel

last: Alvarez-Arguedas

state: Texas

address: 5323 Harry Hines Blvd

department: Internal Medicine

institute: University of Texas Southwestern Medical Center

summary: The nasal, oropharyngeal, and bronchial mucosa are the initial contact points for airborne pathogens like Mycobacterium tuberculosis (Mtb), SARS-CoV-2, and influenza virus. While mucosal surfaces can function as both entry points and barriers to infection, mucosa-associated lymphoid tissues (MALT) facilitate early immune responses to mucosal antigens. MALT contains a variety of specialized epithelial cells, including a rare cell type called a microfold cell (M cell) that functions to transport apical antigens to basolateral antigen-presenting cells, a crucial step in the initiation of mucosal immunity. M cells have been extensively characterized in the gastrointestinal (GI) tract in murine and human models. However, the precise development and functions of human airway M cells is unknown. Here, using single-nucleus RNA sequencing (snRNA-seq), we generated an atlas of cells from the human adenoid and identified 16 unique cell types representing basal, club, hillock, and hematopoietic lineages, defined their developmental trajectories, and determined cell-cell relationships. Using trajectory analysis, we found that human airway M cells develop from progenitor club cells and express a gene signature distinct from intestinal M cells. Surprisingly, we also identified a heretofore unknown epithelial cell type demonstrating a robust interferon-stimulated gene signature. Our analysis of human adenoid cells enhances our understanding of mucosal immune responses and the role of M cells in airway immunity. This work also provides a resource for understanding early interactions of pathogens with airway mucosa and a platform for development of mucosal vaccines.

overall_design: Human adenoid samples collected from 6 donors (age 2 – 14; 3 males and 3 females) from elective adenoidectomy for obstructive sleep apnea. All samples were obtained at the Children’s Medical Center of Dallas.

first: Khadijah

last: Mazhar

first: Andi

last: Wangzhou

first: Ishwarya

last: Sankaranarayanan

first: Gabriela

last: Gaona

first: John

last: Lafin

first: Ron

middle: B

last: Mitchell

first: Theodore

last: Price

first: Michael

middle: U

last: Shiloh


title: 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility [RNA-seq]

city: Philadelphia

first: Khanh

middle: Bao

last: Trang

address: 3615 Civic Center Blvd

department: Human Genetics

institute: Children's Hospital of Philadelphia

summary: The genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but GWAS do not reveal causal variants, effector genes, or the cell types impacted by disease-associated variation. We have generated 3D genomic datasets consisting of promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq and integrated these data with GWAS of 16 autoimmune traits to physically map disease-associated variants to the genes they likely regulate in over 50 human cell types. These 3D maps of gene cis-regulatory architecture are highly powered to identify the cell types most likely impacted by disease-associated genetic variation compared to 1D genomic features, and tend to implicate different effector genes than eQTL approaches in the same cell types. Most of the variants implicated by these cis-regulatory architectures are highly trait-specific, but nearly half of the target genes connected to these variants are shared across multiple autoimmune disorders in multiple cell types, suggesting a high level of genetic diversity and complexity among autoimmune diseases that nonetheless converge at the level of target gene and cell type. Substantial effector gene sharing led to common enrichment of similar biological networks across disease and cell type, however, trait-specific pathways representing potential areas for disease-specific intervention were identified. To test this, we functionally validated squalene synthase, a cholesterol biosynthetic enzyme encoded by the FDFT1 gene implicated in MS and SLE, as a novel immunomodulatory drug target controlling inflammatory cytokine production by human T cells. These data represent a comprehensive resource for basic discovery of gene cis-regulatory mechanisms, and the analyses reported reveal mechanism by which autoimmune-associated variants act to regulate gene expression, function, and pathology across multiple, distinct tissues and cell types.

overall_design: To investigate the expression landscape of different immune cell types, we performed genes expression profile analysis from RNA-seq of different cell types at different stages.

first: Megan

last: Levings

first: Struan

middle: F

last: Grant

first: Andrew

last: Wells


title: Genome-wide methylation profiles of post-mortem tissue samples (human)

status: Public on Nov 06 2025

city: Seoul

first: Hwan Young

last: Lee

address: 103, Daehak-ro, Jongno-gu

country: South Korea

institute: Seoul National University College of Medicine

summary: In this study, genome-wide DNA methylation profiling was performed on post-mortem skeletal muscle tissues obtained from three Korean individuals. A total of 250 ng of genomic DNA from each sample was analyzed using the Illumina Infinium MethylationEPIC BeadChip array (Illumina, San Diego, CA, USA) at Macrogen Inc. (Seoul, Korea).

overall_design: DNA methylation profiling of 3 post-mortem muscle tissue samples was conducted using the Infinium MethylationEPIC Beadchip array.

first: Soo Bin

last: Yang


title: Optineurin Shapes Basal and LPS-Induced Transcriptomes in BV2 Microglia

city: Trieste

first: Maurizio

last: Romano

address: Via A. Valerio 28

department: Department of Life Sciences

institute: University of Trieste

summary: The OPTN gene is linked to neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which are characterized by chronic microglial activation. Optineurin regulates inflammatory signaling, autophagy, and trafficking, but its role in microglia is not well understood. We used bulk RNA sequencing to profile CRISPR-Cas9-mediated optineurin knockout (KO) and wild-type (WT) BV2 microglia under basal conditions and upon LPS stimulation. At baseline, optineurin KO altered approximately 7% of the transcriptome, with a notable downregulation of type I interferon and antiviral pathways. LPS stimulation in wild-type cells triggered a broad transcriptional shift (~35% of genes). This LPS-induced response was blunted in optineurin-deficient microglia, with ~16% of genes changed relative to the KO baseline. Furthermore, LPS-treated optineurin KO microglia notably diverged from LPS-treated wild-type cells, with ~26% differentially expressed genes. Our findings establish optineurin as a key regulator of the microglial transcriptome. Its loss weakens basal interferon-mediated immune surveillance and decouples the canonical inflammatory response from cell cycle arrest upon activation.

overall_design: Bulk RNA sequencing was performed on four conditions: untreated wild-type (CTRL), optineurin knockout (KO), LPS-treated wild-type (LPS), and LPS-treated optineurin knockout (KO_LPS) BV2 cells. Triplicate samples were used for each condition.

first: Sara

last: Cappelli

first: Josip

last: Peradinoviƒá

first: Alessandra

last: Longo

first: Nikolina

last: Mohoviƒá

first: Purba

last: Mandal

first: Cristiana

last: Stuani

first: Jason R.

last: Cannon

first: Priyanka

last: Baloni

first: Benedetta

last: Leoni

first: Gordana

last: Apic

first: Robert R.

last: Russell

first: Emanuele

last: Buratti

first: Ivana

last: Munitic


title: scRNA seq of Pdgfra+ cells from the mouse intestine

status: Public on Nov 05 2025

city: Cambridge

first: Alok

last: Jaiswal

state: MASSACHUSETTS

address: 415 Main Street

institute: The Broad Institute of MIT and Harvard

summary: Sorted PDGFRA+cells  that were lineage-negative for other major intestinal cell type markers (EPCAM1, TER119, CD45, PECAM1) were obtained from the colon of 5 mice. Briefly, mice were given 2.0% (weight/volume) DSS (Thermo Fisher Scientific, #J14489-22) dissolved in water for 7 days for the acute model of DSS. In the chronic model, DSS-administration was followed by a water recovery phase lasting for another 7 days. This cycle was repeated 2 more times, with mice weights being recorded daily.

overall_design: 3 Acute DSS treated vs. 2 Chronic DSS treated  samples from Il11mNG reporter mice

first: Vladislav

last: Pokatayev

first: Daniel

last: Graham

first: Ramnik

last: Xavier


title: IAF scRNA seq

summary: Human fibroblast cells were treated with a combination of fibrotic cytokines (TGF-b and IL-1b) over a time course of 0, 6, 12 and 24 hours. Live cells were collected and submitted to single cell sequencing.


title: 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility [captureC]

first: Khanh

last: Trang

overall_design: To investigate the 3D chromatin conformation landscape of different immune cell types, we performed chromatin contacts profile analysis from Promoter-focused Capture-C of different cell types at different stages.

first: Megan

last: Levings

first: Struan

last: Grant

first: Andrew

last: Wells


first: Pushpinder

last: Bawa

overall_design: To assess the effects of filovirus infection on the human gastrointestinal tract, we exposed induced pluripotent stem cell (iPSC)-derived human colonic organoids (HCOs) to Ebola virus (EBOV) and Marburg (MARV) virus. Bulk RNA sequencing (bulk RNA-seq) was performed on proximal HIOs (n = 3), distal HIOs (n = 3), and mock-infected controls (n = 3) at 1 and 3 days post-infection to identify transcriptomic changes. These findings were further supported by immunohistochemistry and immunofluorescence assays to validate viral infection.

first: Elizabeth Yvonne

last: Flores

first: Aditya

last: Mithal


title: 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility [ATAC-seq]

overall_design: To investigate the chromatin accessibility landscape of different immune cell types, we performed open chromatin regions profile analysis from ATAC-seq of different cell types at different stages.


title: MeCP2 regulates telencephalic development in human cerebral organoids

city: La Jolla

first: Alysson

middle: R.

last: Muotri

address: 2880 Torrey Pines Scenic Drive - Room 3005

institute: UCSD

summary: Human cerebral organoids and telencephalic assembloids derived from iPSC lines: isogenic control and harboring MeCP2 variants associated with Rett Syndrome.

overall_design: Expression profiling by high throughput sequencing

first: Miguel

last: Tenreiro


title: Xenium spatial transcriptomics of human carotid artery plaques

status: Public on Nov 04 2025

city: München

first: Jessica

last: Pauli

state: Bayern

address: Biedersteiner Str. 29

department: Molecular Vascular Medicine

institute: TUM Universitätsklinikum (Klinikum rechts der Isar)

summary: We performed Xenium single cell transcriptomics on 4 plaques with matched controls (8 samples in total) and 8 additional plaques. A total of 16 samples was sequenced with two panels each.

overall_design: Xenium single cell transcriptomics with 2 Panels on 4 plaques with matched controls (8 samples in total) and 8 additional plaques

first: Lars

last: Maegdefessel

last: Garger


title: Single Cell Transcriptomics of human carotid artery plaques V2

summary: We profiled the single-cell transcriptome and analyzed the diversity of cell types present in human atherosclerotic tissue specimens (carotid artery, CAR). Therefore we carried out scRNA-seq from 7 different patients.

overall_design: To profile single-cell transcriptome and analyze the diversity of cell types present in human atherosclerotic tissue specimens (carotid artery, CAR), we carried out scRNA-seq from 7 different patients.


title: Transcriptome analysis of the effect of Armh4 on aging

city: Shenzhen

first: Zhihua

last: Wang

address: No. 12, Langshan Road, Xili Street, Nanshan District, Shenzhen

department: Shenzhen Key Laboratory of Cardiovascular Disease

institute: Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen

summary: Aging is an inevitable process integrating chronological alterations of multiple organs. A growing aging population necessitates feasible anti-aging strategies to deal with age-associated health problems. We previously performed a proteomics analysis in a healthy-aging cohort, and revealed an age-related downregulation of ARMH4. Here we generate a whole-body Armh4-knockout mouse line, and investigate its impact on systemic aging. Under normal feeding conditions, Armh4 deficiency significantly lowers spontaneous mortality and extends maximum lifespan. In the female mice, Armh4 deficiency postpones sexual maturity for one week. At the organ level, the age-related pathologies of the heart, liver, kidney, and spleen are substantially alleviated by Armh4 deletion. Mechanistically, ARMH4 interacts with IGF1R/FGFR1 to sensitize the activation of PI3K-Akt-mTORC1 and Ras-MEK-ERK pathways, consequently promoting protein synthesis and inhibiting autophagy. Moreover, ARMH4 is required for the maintenance of IGF1R/FGFR1 expressions through regulating the transcription factor c-Myc. Therefore, ARMH4 maintains a positive-feedback growth signaling to promote aging.

overall_design: Normal and healthy c57bl/6j young mice and systemic Armh4 gene knockout mice were raised in a stable environment (room temperature 24±3℃; indoor humidity 55±5%), 12-hour light/12-hour dark cycle, fed normal food, and raised to 25 months of age, and divided into WT_Aged group and KO_Aged group. In addition, the feeding environment of WT_Young group and KO_Young group mice was consistent with that of aged mice, and they were raised for 8 weeks, with at least 6 mice in each group. Mice were anesthetized with inhaled anesthetics and killed by cervical dislocation. The heart was immediately dissected and stored at -80°C.  Select 4 independent biological replicate samples from each of the four separate groups, namely WT_Aged, KO_Aged, WT_Young, and KO_Young, to extract RNA. RNA-seq was provided by Beijing Genomics Institute (BGI)

first: Yu

last: Fang

first: Baosen

first: Ningning

last: Guo

first: Jian

last: Lv


title: Transcriptional Dynamics and Chromatin Accessibility in the Regulation of Shade-Responsive Genes in Arabidopsis [ATAC-seq]

city: Lausanne

first: Christian

last: Fankhauser

state: Vaud

address: Batiment Genopode

department: Center for Integrative Genomics

country: Switzerland

institute: University of Lausanne

summary: Accessible chromatin regions host DNA regulatory motives and are highly accessible to the transcription factors and transcriptional machinery. In Arabidopsis, responses to light are heavily regulated at the transcriptional level.  Shade, for example, can limit photosynthesis and is rapidly perceived by phytochromes as a reduction of red to far-red light ratio. Under shade, phytochromes inactivate and allow PHYTOCHROME INTERACTING FACTORs (PIFs) to promote a wide scale genome reprogramming. A strong and fast initial regulation of shade responsive genes is followed by an attenuation of this response under prolonged shade. We wanted to determine if transcriptional response pattern to shade depends on chromatin accessibility. For this we used ATAC-seq to profile the chromatin of seedlings exposed to short (1h) and long (25h) simulated shade. Transcription pattern of most acute shade responsive genes correlates with the rapid increase in PIF levels/activity at 1h, and its decrease at 25h of shade exposure. For a set of acute responding genes, PIFs also modulate chromatin accessibility at their binding sites in response to shade. Our results suggest that permanent state of open chromatin conformation allows PIFs to easily access and recognize their binding motifs, rapidly initiating a burst in gene expression triggered by shade. This transcriptional response primarily depends on a transient increase in stability of PIFs and gene occupancy and is followed by a moderate change of chromatin accessibility.

overall_design: ATAC-seq profiling of 7 day-old seedlings grown in high red:far-red light ratio (HRFR) or exposed to 1h or 25h of low red:far-red light ratio (LRFR). Three replicates of Col-0; pUBQ10::BirA; pUBQ10::NTF and sav3-2; pUBQ10::BirA; pUBQ10::NTF for each condition were collected at ZT3.

first: Sandi

last: Paulišić

first: Alessandra

last: Boccaccini


title: Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice

first: Chenyang

last: Fu

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility [HiC]

first: Khanh

last: Trang

overall_design: To investigate the 3D chromatin conformation landscape of different immune cell types, we performed chromatin contacts matrix profile analysis from Hi-C of different cell types at different stages.

first: Struan

last: Grant

first: Andrew

last: Wells


title: Transcriptional Dynamics and Chromatin Accessibility in the Regulation of Shade-Responsive Genes in Arabidopsis [RNA-Seq]

overall_design: RNA-seq profiling of 7 day-old seedlings grown in high red:far-red light ratio (HRFR) or exposed to 1h or 25h of low red:far-red light ratio (LRFR). Three replicates of Col-0 and pif457 for each condition were collected at ZT3.


title: Major waves of H2A.Z incorporation during mouse oogenesis and preimplantation embryo development

city: Copenhagen

first: Erkut

last: Ilaslan

address: Blegdamsvej 3

department: Department of Cellular and Molecular Medicine

country: Denmark

institute: University of Copenhagen

summary: Epigenomes of mammalian oocytes and embryos undergo major transitions essential for successful development. Here, we provide genome-wide maps of histone variant H2A.Z during twelve stages of mouse oogenesis and preimplantation embryo development and relate it to histone marks and genomic features. This revealed that major waves of H2A.Z incorporation occur early in growing oocytes, forming distinct patterns of maternal, embryonic, and persistent H2A.Z enrichment. Late maternal enrichment is inherited by the zygote, and precedes reduced formation of lamina associated domains and early replication in the maternal genome of 2-cell embryos. Persistent H2A.Z enrichment is strongly associated with CpG islands and H3K4me3 near transcription start sites of active genes, but thousands of maternal and embryonic H2A.Z incorporation sites exist elsewhere, frequently at transposable elements. The persisting H2A.Z enrichments across related developmental stages enable preservation of epigenetic information despite major concurrent changes in H3K4me3, H3K27me3, and DNA methylation. Altogether, this advances our understanding of how histone variants contribute to epigenetic reprogramming during mammalian oogenesis and early development.

overall_design: H2AZ profile in oocytes and early embryos were characterized using picoChIP-seq.

first: Madeleine

last: Fosslie

first: Trine

last: Skuland

first: Michel

last: Choudalakis

first: Mirra

last: Søegaard

first: Jason

middle: A

last: Halliwell

first: Shaista

last: Khan

first: Marie

last: Indahl

first: Maria

last: Vera-Rodriguez

first: Adeel

last: Manaf

first: Annika

last: Geijer-Simpson

first: Rajikala

last: Suganthan

first: Ingunn

last: Jermstad

first: Knut

middle: T

last: Dalen

first: Ragnhild

last: Eskeland

first: Elisabeth

last: Kommisrud

first: Arne

last: Klungland

first: Magnar

last: Bjørås

first: Peter

last: Fedorcsak

first: Gareth

last: Greggains

first: Mika

last: Zagrobelny

first: John

last: Dahl

first: Mads

last: Lerdrup


title: Arabidopsis cationic amino acid transporter (CAT) is a high affinity transporter for a systemic herbicide L-Phosphinothricin

city: Singapore

first: Grace

middle: Zi Hao

last: Tan

address: 1 Research Link National University of Singapore, 03-48

country: Singapore

institute: Temasek Life Sciences Laboratory

summary: L-phosphinothricin (PPT) is a broad-spectrum herbicide, however its transportation mechanisms remain unidentified. Here we present cationic amino acid transporters (CAT) as the high affinity transporter of PPT, explaining the different sensitivities of flowering and non-flowering plants. Comparative analysis between Arabidopsis thaliana and Marchantia polymorpha revealed non-target site mechanisms for PPT resistance in the latter. LC-MS analysis showed minimal PPT uptake by M. polymorpha, while transcriptomic analysis identified four candidate transporters for PPT uptake. Overexpression of AtCAT1 and AtCAT5 in M. polymorpha increased PPT susceptibility and uptake. Protein molecular dynamics simulation revealed the modes of PPT transportation, allowing for mutagenesis strategies to reduce PPT susceptibility. This study reports the first high affinity PPT transporter, AtCAT, and highlights the natural diversity of PPT susceptibility due to transportation.

sample_organism:
Marchantia polymorpha
Arabidopsis thaliana

overall_design: To identify transcriptional response to GS-inhibiting herbicides, RNAseq analysis was perform on Arabidopsis seedlings and Marchantia gemmalings treated with glutamine, phosphinothricin, or methionine sulfoxime for 48h. Untreated plants were used as controls. n=3

middle: Z

first: Daisuke

last: Urano


title: Persistent pneumococcal colonisation in anti-retroviral-treated HIV infection is associated with nasal inflammation

status: Public on Nov 03 2025

city: Blantyre

first: Joseph

middle: Aston

last: Phiri

state: Southern Region

address: Chipatala Avenue

country: Malawi

institute: Malawi Liverpool Wellcome Programme

summary: We have employed a single cell RNA sequencing approach to study the nasal immune and epithelial cells landscape in People Living with HIV (PLHIV) and during the course of anti-retroviral uptake. The landscape ansal immunity is crucial for early control of respiratory pathogens including bacterian and viruses.

overall_design: Cross-sectional observational cohort design recruiting HIV- adults, People Living with HIV on ART for less than three months and people living with HIV on ART for greater than one year. Nasal cells were collected from all the participants using a nasal curette from the inferior turbinate.Single cell suspensions were prepared and libraries were prepared using 10X 5' platform. Samples were sequenced on a NextSeq 5000

last: Aston Phiri

first: Kondwani

last: Charles Jambo


title: GLIS3 RNA-seq

first: Alok

last: Jaiswal

country: USA

summary: Define the transcriptome of fibroblasts perturbed for GLIS3 in response to fibrotic stimuli.

overall_design: IL-11mNG CRISPRko Ctrl/Glis3KO, and IL-11mNG CRISPRa Ctrl/Glis3A fibroblasts were treated with a combination of TGFb and IL1b (10ng/ml) over a timecourse of 24 hours. Cells were collected, RNA isolated, and submitted for bulk RNA-seq.

first: Vladislav

last: Pokatayev

first: Daniel

last: Graham

first: Ramnik

last: Xavier


title: GLIS3 ChIP-seq

summary: Define the DNA targets of fibroblast GLIS3 in response to fibrotic stimuli.

overall_design: IL-11mNG GLIS3-FLAG fibroblasts were treated with a combination of TGFb and IL1b (10ng/ml) over a timecourse of 24 hours. Cells were collected and ChIP Seq was performed. Sheared DNA lysate was incubated with anti-H3K4me3, -FLAG, or -IgG for the procedure.


title: Unveiling distinct storage composition and starch properties in developing indica rice grains via transcriptional profiling and enzymatic activity analysis

status: Public on Nov 01 2025

city: Khon Kaen

first: Maysaya

last: Thitisaksakul

address: Mittrapap Road

department: Biochemistry

country: Thailand

institute: Khon Kaen University

summary: Recently, we observed significant differences in the starch molecular composition and structure between the two Thai indica rice cultivars, RD6 and RD57. However, a comprehensive understanding of the transcriptional regulation of their storage polymers, remains lacking. To address this, we investigated the gene expression patterns and enzymatic activities of key starch and storage protein biosynthetic enzymes in the developing endosperms of these cultivars. The transcriptional profiles of waxy RD6 and high-amylose RD57 rice endosperms were analyzed at 7, 14, 21, and 28 days post-anthesis (DPA). The expression patterns of major differentially expressed genes (DEGs) were cross validated with enzymatic activities and the grain starch and storage protein compositions. Gene expression profiles varied significantly between the RD6 and RD57 rice cultivars, with the most distinct differences observed at 14 days post-anthesis (DPA) and the least at 28 DPA. Temporal dynamics of transcriptome profiles among genes in starch and storage protein biosynthesis revealed active gene expression at 14 DPA and 7 DPA. Collectively, this study provided a comprehensive understanding of the biosynthesis of storage biomolecules through transcriptional profiling of the Thai indica rice. For the breeding and developing new Thai commercial rice varieties with targeted ECQ and health-beneficial traits, understanding the regulatory mechanisms that control starch and storage protein accumulation at both transcriptional and post-translational levels is crucial.

overall_design: RNA-seq profiling of waxy RD6 and high-amylose RD57 rice endosperms at 7, 14, 21, and 28 days post-anthesis (DPA)

first: Wichian

last: Sangwongchai

first: Kwanjeera

last: Wanichthanarak

first: Ammarin

last: In-on


title: Pharmacological rescue of motor neuron health by riluzole in patient-derived motor neurons

status: Public on Nov 02 2025

city: Melbourne

first: Christopher

last: Bye

state: Victoria

address: University of Melbourne

country: Australia

institute: The Florey Institute of Neuroscience and Mental Health

summary: Heterogeneous and predominantly sporadic neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) remain highly challenging to model. Patient-derived induced pluripotent stem cell (iPSC) technologies offer great promise for these diseases, however large-scale studies demonstrating accelerated neurodegeneration from sporadic patients are limited. We generated an iPSC library from 100 sporadic ALS (SALS) patients and conducted population-wide phenotypic screening. SALS patient-derived motor neurons recapitulated key aspects of SALS, including reduced survival, accelerated neurite degeneration correlating with donor survival, transcriptional dysfunction, and pharmacological rescue by riluzole. Here we sought to determine if riluzole treatment reversed the disease process in patient-derived motor neurons by RNAseq profiling of riluzole treated vs untreated motor neurons from 9 ALS donors.

overall_design: RNAseq profiling of patient-derived motor neurons from 9 ALS donors treated with DMSO or riluzole (2.5uM) from day 36 onwards. Samples collected at day neurite collapse reaches 50% of peak health in DMSO treated (LD50).

first: Bye

last: Christopher

first: Qian

last: Elizabeth

first: Lim

last: Katherine

first: Morgan

last: Steven


title: Mpox virus replicates in lung organoids without significantly affecting their cellular function

city: Kyoto

first: Kazuo

last: Takayama

state: Kyoto

address: Shogoin Kawaharacho 53, Sakyo-ku

department: Center for iPS Cell Research and Application

institute: Kyoto University

summary: Patients with mpox may present with a skin rash and mild respiratory symptoms, including sore throat and cough. The genome of the mpox virus (MPXV) has been detected in throat swab specimens from some mpox patients, indicating potential involvement of the respiratory tract. In this study, we used lung organoids to investigate the effects of MPXV infection on the respiratory system by evaluating the viral replication and the infection-mediated host response. MPXV infection resulted in the accumulation of high levels of viral genomes within the cells. H&E staining showed almost no histological differences between MPXV-infected lung organoids and uninfected lung organoids. In addition, RNA-seq analysis revealed that MPXV infection did not significantly alter the gene expression levels of various lung markers. MPXV infection did not change the production of proinflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-beta (IFN-β). These findings suggest that MPXV can replicate in lung organoids without significantly affecting their cellular function.

overall_design: Total RNA was collected from MPXV-infected lung organoids, and then RNA-seq was performed.


title: IsomiR Utility in ALS Prognostication [control]

status: Public on Oct 31 2025

city: ראשון לציון

first: Iddo

last: Magen

state: Not in US

address: בן אליעזר 32, 17

country: Israel

institute: Weizmann Institute

summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. IsomiRs are microRNA (miRNA) isoforms that arise from alternative processing or editing events during miRNA biogenesis. While isomiRs may carry distinct biological and clinical relevance, their potential as cell-free biomarkers in neurodegeneration remains largely unexplored. Here we investigated the prognostic utility of plasma isomiRs in ALS, using next-generation sequencing. We profiled cell-free isomiRs in 154 ALS patients from a British cohort and identified higher levels of one isomiR, let-7g-5p.t, to be associated with longer survival. This finding was independently validated in an international ALS cohort of 200 patients and was in two orthogonal approaches. let-7g-5p.t prognostic utility was comparable to that of neurofilament light chain (NfL) or miR-181. These results establish isomiRs as a novel class of blood-based biomarkers in ALS with potential to refine prognostication in clinical trials for neurodegenerative diseases.

overall_design: Small RNA next-generation sequencing  The molecular experimenters were blinded to the identity of the samples. Total RNA was extracted from 500μl plasma using miRNeasy Micro Kit following the manufacturer's protocol except adding 2.5ml of Qiazol to each plasma sample (Qiagen, #217084). RNA was quantified with a Qubit fluorometer using the RNA Broad Range Assay Kit (Thermo Fisher Scientific, #Q10211). Small RNA next-generation sequencing libraries were prepared using the QIAseq miRNA Library Kit (Qiagen, #331502) from 7.5 ng of total RNA. If RNA concentration was below the limit of detection, 5μl of undiluted RNA were used. Precise linear quantification of miRNAs was achieved by 12-nucleotide long unique molecular identifiers (UMIs). Samples were randomly assigned to the preparation of libraries indexed with QIAseq miRNA NGS 48 Index IL (Qiagen, #331595) and sequenced in batches of 48 or fewer samples. Library concentration was determined with a Qubit fluorometer (dsDNA High Sensitivity Assay Kit, Thermo Fisher Scientific, #Q32854) and library size with TapeStation D1000 (Agilent). Libraries with different indices were multiplexed and sequenced on a NextSeq 500/550 v2 (Illumina, #20024906) or a NovaSeq 6000 flow cell (Illumina, #20028401), with a 75-bp single read or paired-end reads with 6-bp index. FASTQ files were de-multiplexed using the user-friendly transcriptome analysis pipeline. Human miRNAs and isomiRs, as defined by miRBase - V22, were mapped using CLC genomic workbench 22.0 (Qiagen) only to the positive strand. Reads were trimmed in two consecutive fashions; Phred score, Q based error was calculated for every nucleotide, high values reflect poor read quality. A trimming score defined by the subtraction of the error from a threshold of 0.05 was set for each nucleotide. Then, a running sum of the nucleotide errors was calculated per read. The region between the first positive value of the running sum and the highest value of the running sum was kept with non-positive score reads being removed completely. Consecutively, reads’ ends were trimmed to keep the maximum length region containing 2 or fewer ambiguous nucleotides. This was followed by the library’s 3’-adaptors (TGGAATTCTCGGGTGCCAAGG) trimming, with reads that did not contain any adaptors being excluded from downstream analyses. Reads were filtered based on lengths of 15-55 bps. IsomiRs were considered as 2bps changes (insertion, deletion, shift, and mismatch) up/downstream from miRBase reference sequence with a maximum of 2 mismatches allowed in alignment. The algorithm prioritizes perfect matches to reference miRNAs, followed by sequences of increasing mismatch nucleotides. When a sequence aligns equally well to multiple isomiRs, counts are assigned uniformly across all matching forms.

first: Yahel

last: Cohen

first: Ilan

last: Sinai

first: Yehuda

middle: M

last: Danino

first: Joanne

last: Wuu

first: Andrea

last: Malaspina

first: Michael

last: Benatar

first: Eran

last: Hornstein


title: VRK1 can be a novel therapeutic target in small cell neuroendocrine carcinoma of the uterine cervix

city: Suita

first: Satoshi

last: Nakagawa

state: Osaka

address: 2-15 Yamadaoka

department: Osaka University

institute: Department of Obstetrics and Gynecology

summary: Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare and highly aggressive cancer. In this study, we aimed to investigate the potential of vaccinia-related kinase 1 (VRK1) as a therapeutic target for SCNEC and to elucidate its functional mechanisms. VRK1 expression was found to be higher in SCNEC than in other histological types of cervical cancer. In both 3D cell culture and subcutaneous mouse models, shRNA-mediated VRK1 knockdown (shVRK1) exhibited significant antitumor effects. Gene Set Enrichment Analysis of RNA-seq data from the subcutaneous mouse models indicated that the effects of VRK1 are related to responses to external stimuli and mitochondrial pathways. In vitro, mitochondrial membrane potential was significantly decreased under hydrogen peroxide stimulation in shVRK1 cells compared to controls, suggesting that VRK1 knockdown induces mitochondrial dysfunction under external stimuli. In summary, VRK1 may be a promising therapeutic target for SCNEC, particularly through its role in mitochondrial responses to external stimuli.

overall_design: To investigate the function of VRK1, we established HCSC-1 and TC-YIK cells with VRK1 knockdown via shRNA (shVRK1) and corresponding control cells (shCont). These cells were transplanted subcutaneously into mice, and the resulting tumors were excised. Gene Set Enrichment Analysis was then performed on RNA-seq data obtained from these tumors.

first: Mariya

last: Kobayashi

first: Yuji

last: Kamei


title: Accute and repeated DSS exposure induce distinct immune responses with differential relevance to human Ulcerative Colitis

city: Chicago

first: Ronen

last: Sumagin

state: Illinois

address: 303 E Chicago Ave

institute: Northwestern University

summary: Dextran sulfate sodium (DSS)-induced colitis is a widely used model to study ulcerative colitis (UC). However, the extent to which acute versus repeated DSS exposure mimics human disease remains unclear. Using histopathology, flow cytometry, single-cell RNA sequencing (scRNA-seq) and 16S rRNA profiling we compared disease outcomes, immune infiltrate, transcriptional programs and changes in the microbiome in mice subjected to a single (acute) versus two (repeated) DSS cycles. We found that repeated cycles of DSS-induced colitis in mice result in more severe intestinal inflammation compared to a single exposure, with increased PMN and T cell infiltration, mucosal remodeling, and microbiota normalization. Single-cell transcriptomics revealed that acute vs repeated DSS exposure drives differential programs in immune cell subtypes distinctly overlapping with human UC. Overall, our findings suggest that repeated DSS exposure may more accurately models human disease, highlighting its utility for translational IBD research.

overall_design: RNA seq profiling of colonic biopsies of inactive UC patients and colon digest of C57/BL/6J mice during 1 cycle and 2 cycles (2.5%) DSS.

first: Zeinab

last: Dehghani

first: Laura

last: Manzanares

first: Caroline

last: Hernreiter

first: Xingsheng

last: Ren

first: Maya

middle: E

first: Anastasiia

last: Serdiukova

first: Ankur

last: Naquib

first: Stefan

last: Green

first: Joshua

last: Wechsler


title: eIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by small molecules

city: Aurora

first: Neelanjan

last: Mukherjee

state: Colorado

address: Research Complex 1 South, 12801 E 17th Ave

department: Biochemistry and Molecular Genetics

institute: University of Colorado School of Medicine

summary: Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis; effects which are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia inducible factors (HIFs). However, translational effects in hypoxia, that likely precede transcriptional effects, have remained largely unexplored. Using ribosome-profiling, we uncovered a selective translational response in acute hypoxia that is eIF3d/eIF3e-dependent and controls downstream hypoxic responses including HIF1a accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e- and eIF3d-expression signatures are associated with worsened outcomes for breast cancer patients. Finally, we identified a class of novel small molecules that target eIF3e specifically, reducing the translational response to hypoxia and to ER stress, another stressor that is dependent on eIF3d/eIF3e-mediated translation. Our data uncover critical functions for eIF3d/eIF3e in the hypoxic response and identify a potential means to inhibit stress-induced translation, and potentially plasticity and metastasis, mediated by eIF3e.

overall_design: Ribosome profiling and RNA-sequencing from MCF7-SIX1 cells and MDA-MB-231 cells. Cells were treated with etiher 1 hour hypoxia or normoxia and sictrl, si3d, si3e, DMSO, a209 or 8430.

first: Stephen C.

last: Purdy

first: Kate

last: Matlin

first: Christopher

last: Alderman

first: Amber

last: Baldwin

first: Natasha

last: Shrivastava

first: Goksu

last: Sarioglu

first: Somnath

last: Dutta

first: Kristofor J.

last: Webb

first: Arthur

last: Wolin

first: Dillon P.

last: Boulton

first: Annika

last: Gustafson

first: Jyoti

last: Kapali

first: John D.

last: Landua

first: Michael T.

last: Lewis

first: M. Cecilia

last: Caino

first: James C.

last: Costello

first: William

last: Old

first: Xiang

last: Wang

first: Rui

last: Zhao

first: Heide L.

last: Ford


title: Single-cell nucleus ATAC sequencing on colorectal tumor and adjacent nonmalignant tissues

city: Daejeon

first: Inkyung

last: Jung

address: 291 Daehak-ro, Yuseong-gu

institute: KAIST

summary: Single-cell ATAC sequencing data were collected from 24 colorectal tumor and 9 adjacent nonmalignant tissues pooled into 15 libraries. This dataset was generated to investigate the global chromatin accessibility profiles of epithelial, stromal, and immune cells in the colorectal cancer microenvironment. Information on the donors, tissues, libraries, and demultiplexed barcodes are provided in the supplementary data of the cited paper.

overall_design: Single-cell chromatin accessibility profiling by high throughput sequencing

first: Andrew

middle: J

last: Lee

first: Truc Do Thanh

last: Nguyen

first: Woong-Yang

last: Park


title: Nature-inspired IL-1 targeted therapy to treat chronic inflammatory diseases

city: Worcester

first: Yen

last: Yang

state: MA

address: 366 Plantation st, NERB / N9-3004D

department: Genetic and Cellular Medicine

institute: Umass Chan Medical school

summary: The interleukin-1 (IL-1) pathway drives inflammation in rheumatoid arthritis (RA) and other autoinflammatory diseases. We developed a recombinant adeno-associated virus (rAAV) gene therapy that delivers a secreted human IL-1 receptor antagonist (sIL-1Ra) under an inflammation-inducible promoter. This vector responds to pro-inflammatory cytokines and BMPs enriched in inflamed joints, enabling on-demand sIL-1Ra production. In mouse models of RA and IL-1Ra deficiency, inflammation-inducible sIL-1Ra reduced IL-1 signaling, immune cell activation, inflammatory gene expression, joint swelling, and bone destruction. A single systemic dose provided long-lasting therapeutic benefit, supporting this approach as a targeted treatment for chronic inflammatory diseases.

overall_design: Synovial tissue was collected from SKG mice (N=3 per group) treated systemically with either an inflammation-inducible rAAV expressing secreted human IL-1 receptor antagonist (sIL-1Ra) or a matched control vector. Total RNA was extracted, bulk RNA-seq libraries were prepared, and sequencing was performed to compare transcriptomes between sIL-1Ra and control groups.

first: Yeon-Suk

first: Mi-Jeong

last: Kim

first: Sachin

last: Chaugule

first: Emma

last: Mayer

first: Ngoc

last: DeSouza

first: Hong

last: MA

first: June

last: Xie


title: Reduced expression of UPF1 promotes tumor progression through stabilizing COX-2 mRNA in nasopharyngeal carcinoma

city: Guangzhou

first: zixuan

last: chen

state: Guangdong

address: 651 Dongfeng Road East, Yuexiu District, Guangzhou, P.R. China

institute: Sun Yat-sen University Cancer Center

summary: Nonsense-mediated mRNA decay (NMD) is conserved mRNA surveillance pathway that targeted and degraded one-third of aberrant and non-aberrant cellular transcripts. Recently, growing evidences have shown that NMD pathway is implicated in multiple cancer types. However, the activity and function of NMD in nasopharyngeal carcinoma (NPC) remains unclear. Here we demonstrated that the expression level of the core NMD factors UPF1 (up-frameshift) was significantly downregulated in NPC tissues compared with adjacent noncancerous tissues and predicted poor prognosis. Knockdown of UPF1 expression enhanced tumor growth and metastasis of NPC cells in vitro and in vivo. UPF1 down-regulated genes revealed by RNA sequencing were selectively upregulated in NPC tissues. COX-2 and PD-L1 were identified as NMD targets. UPF1 knockdown activated ERK/MAPK and JAK2/STAT3 pathways through stabilizing COX-2 in NPC cells. Importantly, co-culture with UPF1 knockdown NPC cells promotes M2 polarization and migration of macrophages, and suppressed proliferation and activation of CD8+ T cell. Our findings suggested that UPF1 expression level and NMD efficiency were impaired in NPC tissues, which contributed to tumor progression and immune modulation.

overall_design: RNA was extracted from UPF1 overexpressing HK1 cells, UPF1 knockdown (UPF1-KD) 6-10B cells, UPF1 overexpressing 5-8F cells, Emetine treated 5-8F cells and their corresponding control cell lines.

first: Chun

last: Wu

first: Ruowen

last: Xiao

last: Sun

first: Shijuan

last: Mai