title: Alternative Anastrozole Target Protects Neurons in Preclinical Models of Inherited Tauopathy

city: Genova

first: Chiara

last: Pedicone

address: Largo Rosanna Benzi, 10

department: Neuroscienze Sperimentali

country: Italy

institute: IRCCS Azienda Ospedaliera Metropolitana Policlinico San Martino

summary: Tauopathies, including Alzheimer's disease, are neurodegenerative diseases characterized by the pathological aggregation of the microtubule-associated protein Tau (MAPT).  This study explores the neuroprotective properties of anastrozole, a clinical aromatase inhibitor, in both a Drosophila tauopathy model expressing human MAPTR406W and isogenic pairs of human induced pluripotent stem cell -derived cortical neurons expressing MAPT mutations. Initially identified through a Drosophila drug screen, anastrozole significantly reduced oxidative stress and Tau phosphorylation in neurons, independent of its aromatase inhibitory action. Further investigation revealed that anastrozole does not exert its protective effects through cholesterol metabolism or aromatase inhibition. Instead, screening in Drosophila identified CYP4V2 as a potential unintended target.  Reducing its expression in MAPTR406W neurons recapitulated the protective effects against oxidative stress-mediated cell death. These findings position anastrozole and its off-target CYP4V2 as novel therapeutic avenues  for Tauopathies and possibly in Alzheimer’s and related dementias by reducing Tau phosphorylation and oxidative stress.

overall_design: Triplicate samples for each condition. Anastrozole treated or control (DMSO) treated cells from WT or MAPT R406W mutant cells

first: Kathryn

last: Bowles

first: Sarah

last: Weitzman

first: Alison

last: Goate


title: A PAI-macrophage axis in pancreatic cancer heterogeneity and immune evasion

status: Public on Jul 20 2026

city: New York

last: Falcomatà

address: 1470 Madison Ave

country: USA

institute: Icahn School of Medicine at Mount Siania

type: Expression profiling by high throughput sequencing

summary: Pancreatic ductal carcinoma (PDAC) is characterized by a highly immunosuppressive, ECM-rich microenvironment, yet tumors display striking heterogeneity. This raises the question of whether immune resistance is a global tumor property or organized within spatially restricted niches. Using Perturb-map spatial functional genomics, we determine how different genes shape the growth and cellular environments of PDAC clones across space and time. This revealed early gene-driven remodeling of local immune neighborhoods preceding late-stage spatial clonal dominance. We identify SERPINE1 (PAI1) and SERPINB2 (PAI2) as dominant regulators of tumor microenvironment control and immune evasion. These SERPINs promote stabilization of fibrin-rich ECM niches that spatially retain and program macrophages toward immunosuppressive states while excluding cytotoxic T cells. Loss of Serpine1 or Serpinb2, or pharmacologic inhibition of PAI1 or CD18, improves tumor control and synergizes with anti-PD-1. Multimodal spatial analysis of patient tumors revealed that immunosuppressive niches form around rare SERPINB2- and SERPINE1-expressing PDAC subpopulations, dominated by SPP1+MARCO+ macrophages. These findings identify cancer-derived SERPINE1/B2 as local spatial organizers of immune suppression, linking tumor-intrinsic heterogeneity to local microenvironmental control and immunotherapy resistance in PDAC.

overall_design: Mouse pancreatic cancer cells were othotopically implanted in the pancreas of immunocompetent syngeneic mice. Resulting tumors from control knockout (KO), Serpinb2 KO and Serpine1 KO  were dissociated and the live cells were analyzed by scRNA-seq.

first: Brian

middle: D

last: Brown


title: Syntaxin Binding Protein 1 regulates the alternative splicing events related to DNA repair  in MDA-MB-231cells

city: Wulumuqi

first: Meng

last: Zhang

state: Xinjiang province

address: Affiliated Tumor Hospital of Xinjiang Medical University

country: China

summary: Breast cancer has emerged as a prevalent form of cancer globally, particularly triple-negative breast cancer. The high prevalence and malignant characteristics of this condition are associated with a variety of environmental factors and molecular influences. Syntaxin Binding Protein 1 (STXBP1) is a transmembrane transport protein predominantly expressed in the brain, playing a crucial role in regulating neurotransmitter release. The low expression levels of STXBP1 are positively correlated with poor prognosis of breast cancer. However, the mechanisms by which STXBP1 contributes to the development of breast cancer remain unclear. In this study, we conducted an overexpression of STXBP1 in triple-negative breast cancer cells (MDA-MB-231) and subsequently assessed its impact on cellular characteristics. Following this, we employed transcriptome sequencing (RNA-seq) technology to investigate the downstream targets associated with STXBP1 overexpression. In MDA-MB-231 cells, the overexpression of STXBP1 significantly inhibited cell proliferation and enhanced apoptosis levels. Through an analysis of RNA sequencing data, we discovered that STXBP1 globally regulates both the expression and alternative splicing profile in MDA-MB-231 cells by modulating 111 differentially expressed genes (DEGs) and 1161 regulated alternative splicing events (RASEs). STXBP1 plays a crucial role in regulating the splicing patterns of numerous DNA repair-related genes, including USP48 and PLEC. Finally, we validated the expression changes of these genes and alternative splicing events in key pathways through RT-qPCR analysis. In addition, we conducted an overlap analysis on the transcriptome data of radiotherapy breast cancer cells alongside our own dataset, which revealed 21 differential alternative splicing events. Notably, this includes the DNA repair-related gene UBE21, whose expression patterns were corroborated by RT-qPCR experiments. We speculate that STXBP1 may play a role in the radiation resistance process of triple-negative breast cancer (TNBC) by regulating the alternative splicing of genes associated with DNA repair. To summarize, this study thoroughly investigated the downstream targets and functions of STXBP1 in breast cancer cells, elucidating the molecular mechanisms underlying STXBP1's anti-tumor properties in relation to breast cancer. These molecular targets have the potential to serve as promising avenues for the treatment of breast cancer, particularly in the case of triple-negative breast cancer.

overall_design: MDA-MB-231 cells with excessively expressed STXBP1 were used to filtrate different expression genes (DEGs) and analyze for STXBP1-regulated AS by RNA-seq. Next , ASEs were validated using RT-qPCR.

first: Xiaoxue

first: Qian

last: Rou

first: Ying

last: Liu

first: Ailifeire

last: Abudujiapaer

first: Minghui

last: Li

first: Huaixiong

last: Wang

first: Fang

last: Cheng


title: ZFP36L2 orchestrates stress-adaptive plasticity in intestinal regeneration and colorectal cancer metastasis (ActDseq)

first: Qingwen

last: Jiang

state: NY

address: 417 East 68th Street, 1725

institute: memorial sloan kettering cancer center

summary: Actinomycin D pulse-chase RNA sequencing (ActD-seq) was used to measure ZFP36L2-dependent mRNA decay rates in two patient-derived colorectal cancer (CRC) liver metastasis organoid lines (MSK107Li and OKG146Li). Organoids expressing a doxycycline-inducible short hairpin RNA targeting ZFP36L2 (shZFP36L2) or a non-targeting control (shCtrl) were cultured for 5 days with 2 μg/mL doxycycline, then treated with or without 5 μg/mL Actinomycin D (ActD) for 5 hours to block de novo transcription. Total RNA was extracted using the RNeasy Mini Kit (Qiagen), and strand-specific mRNA libraries were prepared using the TruSeq Stranded mRNA Kit and sequenced on the Illumina NovaSeq 6000 (PE100). Decay rates were quantified by comparing transcript abundance between ActD-treated and untreated conditions within each knockdown condition; ZFP36L2-dependent decay was calculated as the differential decay rate between shZFP36L2 and shCtrl. ZFP36L2 knockdown significantly stabilized stress-associated transcripts, consistent with ZFP36L2 promoting post-transcriptional decay of AU-rich stress-response mRNAs.

overall_design: Patient-derived colorectal cancer organoids MSK107Li and OKG146Li expressing control shRNA or ZFP36L2-targeting shRNA were treated with or without 5 μg/mL Actinomycin D for 5 hours on day 5 and subjected to RNA-seq to profile ZFP36L2 dependent mRNA decay.

first: Karuna

last: Ganesh

first: Jura

last: Pintar

first: Cyrus

middle: L

last: Tam


title: DNA hydroxymethylation landscape and mitochondrial DNA in lung fibroblasts exhibit specific signatures of single- and multi-fraction alpha-particle radiation

city: Chalk River

first: Richard

middle: B.

last: Richardson

state: Ontario

address: 286 Plant Rd

department: Radiobiology and Health

country: Canada

institute: Canadian Nuclear Laboratories

type: Methylation profiling by high throughput sequencing

summary: Alpha (α)-radiation is a genotoxic and epigenotoxic agent capable of increasing cancer and other health risks. Human exposure to α-radiation to unsafe levels can occur as a result of a single exposure from a nuclear incident or repetitive exposures via inhalation of naturally occurring radon gas that accumulates in enclosed spaces. DNA hydroxymethylation (DNAhm), an intermediary step between DNA methylation (DNAm) and demethylation, is an understudied epigenetic event that can modify gene expression. The human lung is susceptible to single and multiple α-radiation events, yet the DNAhm changes induced in this tissue remain unexplored. The genomic-wide DNAhm profile was examined in the 64 α-irradiated human embryonic lung fibroblast samples from our 2023 methylome study. These cells were irradiated to seven doses (N=4 per dose) of americium-241 ranging from 2 mGy to 2.2 Gy, using two exposure regimens, single-fraction (SF – total dose given at once), and multi-fraction exposure (MF – total dose equally distributed over 14 consecutive days). We report that SF and MF α-irradiation primarily increased DNAhm levels, with more alterations observed following the MF exposure: the gene body region being more susceptible to these alterations. The genes with increased DNAhm levels due to the MF exposure, contrarily to the SF, led to a profound disruption of the inflammatory response and other cellular pathway-based biomarkers of radiation in the α-irradiated cells. We also detected DNAhm changes in key genes encoding enzymes involved in DNAm / demethylation processes, which supports the previous DNAm findings. Similar to DNAm, MF α-irradiation induced a greater number of DNAhm aging changes. Compared to equivalent SF doses, the MF pro-oxidant α-irradiation also resulted in more mitochondrial damage, specifically in the hydroxymethylome of nuclear-encoded mitochondrial genes and the mitochondrial DNA copy number. Although at equivalent doses, SF and MF α-radiation exposures induce radically different effects on the DNAhm and mitochondrial DNA. The DNAhm changes help explain the effects observed in our 2023 methylome study. These findings prove that environmental exposure regimens are a major consideration when assessing DNAm and DNAhm biomarkers and the potential health effects of a pro-oxidant such as α-radiation.

overall_design:
We first irradiated primary lung fibroblast cells to seven doses of americium-241 α-sources ranging from 2.0 to 2,200 mGy using two exposure regimens, a single-fraction where the total dose was given at once, and a multi-fraction method, where the total dose was equally distributed over 14 consecutive days. The irradiation per dose for each regimen was independently conducted in 4 biological replicates. We then performed hydroxymethylated DNA immunoprecipitation (hMeDIP) coupled with sequencing.
The input files were used for the differential analysis can be found in the PRJN1010795.

first: Marilyn

middle: N

last: Vera-Chang

first: John

middle: M

last: Danforth

first: Marilyne

last: Stuart

first: Marjorie

last: Brand

first: Aaron

middle: G

last: Goodarzi

middle: B


title: PACAP-PAC1R signaling in the PSTh mediates stress-induced anxiety-like behavior in mice

city: Hangzhou

address: 866 Yuhangtang Road

institute: Zhejiang University

summary: Stress represents a major risk factor for anxiety disorders, yet the underlying molecular substrates through which stress causes anxiety remain elusive. We employed an established stress paradigm to induce anxiety-like behaviors in mice and found that stress causes robust and sustained activation of glutamatergic neurons in the parasubthalamic nucleus (PSTh). Moreover, inhibition of those neurons significantly reduced anxiety-like behavior in stressed animals. RNA sequencing revealed that the pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1R, encoded by Adcyap1r1) is enriched in the PSTh. Ex vivo patch-clamp recordings showed that PACAP, an endogenous agonist of PAC1R, increases the excitability of PSTh neurons. Interestingly, pharmacological blockade of PAC1R within PSTh was sufficient to prevent anxiety by stress. These findings suggest that stress induces sustained activation of PSTh neurons PACAP-PAC1R signaling, ultimately leading to anxiety-like state.

overall_design:
RNA-seq profiling of PSTh tissues from naive C57BL/6 mice for exploring the molecular substrate that maintains the hyperactivity of PSTh glutamatergic neurons following stress
Please note that the samples are only obtained from naive mice, observing the gene expression within the PSTh brain region under physiological conditions. The stressed group was not involved in this sequencing experiment. Subsequently, based on the sequencing results, we conducted multiple behavioral experiments to determine whether some specific genes which are abundantly expressed in the PSTh atrribute to stress-induced anxiety.

first: Huan

first: Han

last: Xu

first: Jun


title: A highly efficient method to differentiate CGRP-expressing peptidergic nociceptors from human induced pluripotent stem cells

city: Cardiff

first: Viola

last: Volpato

address: Maindy Rd

department: UK DRI

country: United Kingdom

institute: Cardiff University

summary: Human cellular models of disease developed using induced pluripotent stem cells (iPSC) have enabled wide-ranging research from investigation of human disease mechanisms to phenotypic drug screens. Pain disorders such as neuropathic pain and headache remain areas of considerable unmet need and are considered high risk by pharma. Human iPSC-derived sensory neurons have already been used to accelerate translational research but the current differentiation protocols produce non-peptidergic nociceptors. We demonstrate for the first time the robust differentiation of hiPSC into peptidergic nociceptor lineage with high yield. These nociceptors express CGRP and TRPV1 whilst the non-peptidergic marker RET was completely absent. Functionally, the nociceptors show functional maturity including the expression of TTX-resistant currents and responding to TRPV1 and TRPA1 agonists. Importantly, they were able to release CGRP basally and upon stimulation by an inflammatory soup, which was inhibited upon the application of the 5-HT1B/1D/1F agonist, sumatriptan and topiramate, a migraine prophylactic drug. Overall, we report the successful generation of a novel in vitro functional peptidergic nociceptor model which will allow investigation of disease mechanisms in pain and for the development of new effective pain therapies.

overall_design: iPSC-derived TG nociceptors from a healthy donor cell line were analysed using scRNA sequencing.


title: Dissecting the transcriptome of Parkin (PRKN)-linked Parkinson’s disease using 2D and 3D hiPSC-neuronal models

city: Bozen/Bolzano

first: Christian

middle: X

last: Weichenberger

state: BZ

address: Drususallee/Viale Druso 1

department: Institute for Biomedicine

institute: Eurac Research

summary: Mutations in the Parkin (PRKN) gene are the most common known cause of autosomal recessive early-onset Parkinson’s disease (PD), and Parkin dysfunction represents a risk factor for idiopathic PD. Parkin is an E3 ubiquitin ligase, involved in protein quality control and the removal of damaged mitochondria. Here, we generate human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic neurons using both a 2D differentiation protocol and our recently developed 3D method based on the microencapsulation of hiPSCs in small alginate/fibronectin beads. The transcriptional signature of cells from PD patients carrying PRKN mutations is evaluated at the neuronal stage and during the differentiation process. Analyses of mutation-specific gene sets and associated pathways reveal multiple biological processes implicated in PRKN-pathology, including synaptic and metabolic function, inflammation, and intracellular trafficking, reflecting a layered disease development. These data map the contribution of Parkin in early PD pathogenesis and progression before overt neurodegeneration.

overall_design: mRNA profiles of 3D and 2D cultured hiPSCs differentiating to midbrain dopaminergic neurons at T0, day10, day20 and day35.

first: Alessandra

last: Zanon

first: Emanuela

last: Kerschbamer

first: Diana

middle: A

last: Riekschnitz

first: Valentina

last: Gilmozzi

first: Greta

last: Laurenti

first: Martin

last: Lang

first: Anne

last: Grünewald

first: Philip

last: Seibler

first: Peter

middle: P

last: Pramstaller

first: Andrew

last: Hicks

first: Irene

last: Pichler


title: Single cell gene expression profiling of renal cell carcinoma

city: Montréal

first: Hamed

last: Najafabadi

state: Québec

address: 740 Dr. Penfield Avenue

department: Human Genetics

institute: McGill University

summary: This dataset profiles intra-tumor heterogeneity in renal cell carcinoma using single-cell gene expression analysis. Single-cell transcriptomic profiles were generated to characterize malignant and non-malignant cell populations and to enable comparative analyses between primary and metastatic disease states. Gene expression data were used to derive gene programs that capture transcriptional heterogeneity among renal cell carcinoma cells.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
Single-cell RNA sequencing was performed on 21 renal cell carcinoma specimens using the 10x Genomics platform. The cohort includes four major renal cell carcinoma subtypes: 16 clear cell renal cell carcinomas, 2 papillary renal cell carcinomas, 1 chromophobe renal cell carcinoma, 1 clear cell papillary renal cell tumor, and 1 unclassified case. Samples include 12 primary tumors and 9 metastatic tumors, derived from 16 patient tumors and 5 patient‑derived xenograft models originating from primary sites or metastases to the brain and lung.

***************************************************************
Raw files for human/patient samples are being made available in EGA (https://www.ebi.ac.uk/ega/) for controlled access to the personally identifiable sequence data.
***************************************************************

first: Ariel

last: Madrigal

first: Minjun

last: Kim

first: Zohreh

last: Mehrjoo

first: Yasser

last: Riazalhosseini

middle: S


title: Single-cell RNA-seq of sorted microglia from aged Grn KO mice [HEX000661]

city: South San Francisco

first: Thomas

last: Sandmann

email: genomics@dnli.com, sandmann@dnli.com

state: California

address: 161 Oyster Point Blvd

institute: Denali Therapeutics

summary: Microglia were isolated from aged (2yr) WT and Grn KO mouse brains and 10x Genomics single-cell RNA-seq was performed.

overall_design: Microglia (CD11b+/CD45+/CD44-/CD163-/Ly6G-) were sorted from WT or Grn KO 2-year-old mice (5 mice/genotype) after multiplexing with Cell Multiplexing Oligos (CMOs) and captures on two GEMs for 10x Genomics scRNA-seq.

first: Leon

last: Tejwani

first: David

last: Tatarakis

first: Connie

last: Ha

first: Gilbert

last: Di Paolo


title: Gene expression profiling of A498 clear cell renal cell carcinoma cells following HIF1A and HIF2A knockdown

summary: This dataset investigates hypoxia-associated transcriptional regulation in clear cell renal cell carcinoma. Following the identification of hypoxia-related gene programs in malignant cells, siRNA-mediated knockdown of HIF1A, HIF2A, or both was performed in A498 cells. RNA sequencing and differential gene expression analysis were used to identify gene signatures specifically regulated by HIF1A or HIF2A.

overall_design: RNA sequencing was performed on A498 clear cell renal cell carcinoma cells transfected with control siRNA or siRNAs targeting HIF1A, HIF2A, or both genes. Gene expression differences between control, single knockdown, and double knockdown conditions were assessed by differential expression analysis.

first: Elham

last: Moslemi


title: Effect of constitutive Grn KO on BMDM transcriptome [HEX000747_BMDM]

summary: WT and Grn knockout BMDMs were cultured and bulk RNA-seq was performed.

overall_design: WT or Grn knockout BMDMs (4 biological replicates/genotype) were cultured for 3 days and total RNA was extracted and processed for bulk RNA-seq.


title: Effect of lysosomal acidification on Grn knockout primary microglia transcriptome [HEX000747_MG]

summary: WT or Grn knockout primary mouse microglia were treated with endolysosomal acidifier rimeporide and bulk RNA-seq was performed.

overall_design: WT or Grn knockout primary microglia (4 biological replicates/genotype) were treated with DMSO or 2uM rimeporide for 72h and total RNA was extracted and processed for bulk RNA-seq.


title: Targeting EHMT2 Enhances NK Cell Maturation and Antitumor Activity [CUT&Tag]

first: Xinhua

last: Liu

state: Zhejiang

address: NO.2318, Yuhangtang road

department: School of Basic Medicine

institute: Hangzhou Normal University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Integrated RNA-seq and H3K9me2 CUT&Tag profiling reveal that Ehmt2 loss reduces the repressive histone mark H3K9me2 and derepresses transcriptional programs associated with NK cell differentiation and cytotoxicity.

overall_design: Natural killer (NK) cells isolated from wild-type (WT) and EHMT2ΔNK mice were analyzed by RNA-seq and CUT&Tag-seq. NK92MI cells were cultured in the presence of either DMSO or the EHMT2 inhibitor BIX01294, followed by RNA-seq analysis.

first: Minghang

last: Yu

first: Yang

last: Li

first: Xi

last: Wang


title: Transcriptional response of BMDMs to CRISPR KO of key lysosomal genes [HEX000527]

summary: WT BMDMs were nucleofected with sgRNA/Cas9 RNPs to induce knockouts of genes encoding lysosomal proteins of interest, and bulk RNA-seq was performed at day 4 and d13 post-CRISPR.

overall_design: WT BMDMs (5 biological replicates) were treated sgRNA/Cas9 RNPs to target Rosa26 (control), Atp6v1a, Npc1, Pik3c3, Ctsd, Grn, or Trem2 to induce targeted knockouts & loss of target proteins. Cells were kept in culture for 4 or 13 days post-CRISPR and total RNA was extracted and processed for bulk RNA-seq.


title: Targeting EHMT2 Enhances NK Cell Maturation and Antitumor Activity [RNA-Seq]


title: Aberrant activation of Wnt signaling in astrocytes mediates neuroinflammation- induced impairment of cholesterol homeostasis and myelinogenesis

first: Zhang

last: Jiannan

address: cangqian street

institute: Hangzhou normal university

summary: Neuroinflammation often disrupts cerebral cholesterol homeostasis and leads to white matter damage and demyelination. However, the molecular mechanisms underlying these defects have remained enigmatic. In this study, we report that inflammation significantly activates Wnt signaling in astrocytes and induces astrocytic expression of SREBF2 protein, a key transcription factor for cholesterol synthesis, through direct binding of β-catenin/LEF1 complexes to the promoter region of Srebf2. The astrocytic Wnt signaling activation simultaneously inhibits the expression of APOE, the critical apolipoprotein for cholesterol efflux, resulting in a reduced cholesterol supply from astrocytes to oligodendrocytes. The extracellular cholesterol supply is essential for the activation of myelin gene expression by MYRF transcription factor in oligodendrocytes. Moreover, the defective oligodendrocyte differentiation and myelin gene expression caused by astrocytic Wnt activation in transgenic mice can partially be rescued by chemical-enhanced Apoe expression.  Our findings have uncovered a novel regulatory pathway of “inflammation–Wnt signaling–cholesterol metabolism–myelin integrity”, shedding new light on the molecular mechanisms underlying inflammation-induced demyelinating diseases and future therapeutic strategies.

overall_design: In this study, primary oligodendrocyte culture was performed using postnatal day 1 (P1) rats. The cells were divided into three control groups and three 0.01 mM water‑soluble cholesterol treatment groups.

first: Jiannan

last: Zhang

first: Jiaru

last: Zheng

first: Yi

last: Ai

first: Junlin

last: Yang

first: Jingwei

last: Zhao

first: Mengsheng

last: Qiu

first: Kang


title: Transcriptional response of WT and Trem2 KO BMDMs to lysosomal alkalinization [HEX000434]

first: Thomas

last: Sandmann

summary: WT and Trem2 KO BMDMs were treated with BafA1 and bulk RNA-seq was performed.

overall_design: WT or Trem2 KO BMDMs (3 biological replicates) were treated with DMSO or 25nM BafA1 for 22h and total RNA was extracted and processed for bulk RNA-seq.

first: Leon


title: Transcriptional response of mouse primary microglia to lysosomal alkalinization [HEX000413]

summary: WT mouse primary microglia were harvested and treated with BafA1 for increasing durations and bulk RNA-seq was performed.

overall_design: WT primary microglia (3 biological replicates) were treated with DMSO or 50nM BafA1 for 1, 7, 14, or 22h and total RNA was extracted and processed for bulk RNA-seq.

last: Tejwani

first: Connie


title: L-DOPA treatment promotes sustained neurovascular and synaptic homeostasis in the diabetic retina

city: Atlanta

first: Eli

last: Chlan

state: GA

address: 1365 Clifton Rd N E Building B

institute: Emory University

summary: Purpose: Previous work has shown a sustained protective effect of levodopa (L-DOPA) on retinal function in early-stage diabetic retinopathy in humans. Here, we quantify neurovascular function, investigate the longevity of L-DOPA treatment for sustained retinal protection, and assess gene expression changes to identify underlying biology in a diabetic mouse model. Methods: After confirming retinal functional deficits in streptozotocin (STZ)-induced diabetic mice using electroretinogram (ERG) and optomotor response (OMR), control and diabetic mice were treated with: 1) L-DOPA/carbidopa for four weeks (continuous), 2) two weeks of L-DOPA/two weeks of washout, or 3) vehicle for four weeks. During the final two weeks of treatment, ERG and OMR testing was repeated and the vasodilative response to photic flicker stimulus was measured to evaluate neurovascular coupling. Following retinal extraction, bulk RNASeq analyses of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and gene ontology (GO) were used to relate neurovascular functional protection with retinal gene expression. Results: L-DOPA treatment improved ERG oscillatory potential timing and OMR responses in diabetic mice, with improvements maintained during the washout period. Flicker-induced venule vasodilative response also showed sustained improvement in the diabetic L-DOPA washout group. DEGs in the diabetic retina were similar across L-DOPA treatment groups.  WGCNA revealed that L-DOPA treated diabetic mice had specific gene modules associated with synapse function and cytoskeletal components that correlated with L-DOPA-induced retinal function protection. Conclusions: L-DOPA treatment restored and sustained protection of retinal neurovascular function in early-stage diabetic retinopathy in mice. These improvements in function were associated with transcriptional changes related to retinal synapse activity and cytoskeletal integrity.

overall_design: Male mice aged to 4 months were randomly assigned to one of the two groups: control or diabetic. Diabetic induction occured via five-day, low-dose (50 mg/kg) intraperitoneal injection of STZ. Once hyperglycemia was confirmed in diabetic mice, mice were monitored for development of early deficits in visual and retinal function (OMR and ERGs respectively). Once deficits manifested (average 7 weeks post-hyperglycemia), all mice were randomly assigned treatment or vehicle groups. The treatment group was given L-DOPA orally in sweetened condensed milk, with treatment group further split into random assignment of continuous treatment (5 mg/kg or 20 mg/kg L-DOPA daily for four weeks) or washout treatment (20 mg/kg L-DOPA daily for two weeks followed by only vehicle for two weeks). In total, there were six experimental groups: Ctrl+Veh, Ctrl+Cont(Continuous), Ctrl+Wash(Washout, DM+Veh, DM+Cont, DM+Wash. Retinal and visual function was continuously assessed on a weekly basis. At the end of the four weeks of treatment or vehicle, animals were sacrificed by cervical dislocation and retina were extracted and flash frozen.

first: Chenxing

first: Katie

last: Bales

first: Levi

last: Wood

first: Machelle

middle: T

last: Pardue


title: Transcriptional response of mouse BMDMs to diverse lysosomal stressors [HEX000414]

summary: WT mouse BMDMs were treated with various drugs that impair different lysosomal properties for increasing durations and bulk RNA-seq was performed.

overall_design: WT BMDMs (5 biological replicates) were treated with DMSO, 25nM BafA1, 6uM U18666A, 2uM VPS34IN1, 50uM E64 + 50uM leupeptin + 50uM pepstatin (E/LP), or 200ug/mL monosodium urate (MSU) for 1, 7, or 22h and total RNA was extracted and processed for bulk RNA-seq.

last: Ha

first: Gilbert

last: Di Paolo


title: NAT10 Promotes Vascular Remodeling via mRNA Ac4c Acetylation

city: Fuzhou

first: Cheng

last: Yu

state: Fujian

address: 29 Xinquan Road, Gulou District, Fuzhou City, Fujian Province

institute: Affiliated Union Hospital of Fujian Medical University

summary: Vascular smooth muscle cells (VSMCs) phenotype switching is a pathological hallmark in various cardiovascular diseases. N4-acetylcytidine (ac4C), catalyzed by N-acetyltransferase 10 (NAT10), is well conserved in the enzymatic modification of RNA. NAT10-mediated ac4C acetylation is involved in various physiological and pathological processes, including cardiac remodeling. However, the biological functions and underlying regulatory mechanisms of mRNA ac4C modifications in vascular diseases remain elusive. By combining in vitro and in vivo vascular injury models, we identified NAT10 as a crucial protein involved in the promotion of postinjury neointima formation as well as VSMCs proliferation. The potential mechanisms of NAT10 in vascular neointima formation were clarified by RNA sequence (RNA-seq), acetylated mRNA immunoprecipitation sequence (acRIP-seq), and RNA binding protein immunoprecipitation sequence (RIP-seq). NAT10 and ac4C modification were upregulated in injured human and rodent arteries. Deletion of NAT10 in VSMCs effectively reduces postinjury neointima formation and VSMCs phenotype switching. Further RNA-seq, RIP-seq, and acRIP-seq revealed that NAT10, by its ac4C modification, directly interacts with genes, including integrin-β1 (ITGB1) and collagen type I alpha 2 chain (Col1a2) mRNAs. NAT10-mediated ac4C consequently increased ITGB1 mRNA stability and its downstream focal adhesion kinase (FAK) signaling, thereby directly influencing the proliferation of VSMCs and vascular remodeling. The regulation of NAT10 on VSMC phenotype is of translational significance because administration of remodelin, a NAT10 inhibitor, effectively prevents neointima formation by suppressing VSMCs proliferation and downregulating of ITGB1 expression and deactivating its FAK signaling.  Our study reveals that NAT10 promotes vascular remodeling via mRNA Ac4c acetylation, which may be a promising therapeutic target against vascular remodeling.

overall_design: To investigate the function of NAT10 in the regulation of vascular smooth muscle cells prolieration, migration, we performed acRIP-seq and RNA-seq from primary rat vascular smooth muscle cells (Ad-shRNA-con and Ad-shRNA-NAT10, with three biological repeats per group) by Epibiotek (Guangzhou, China). NAT10-RIP-seq was performed from rat primary vascular smooth muscle cells (three biological repeats) conducted by Gene Denovo Biotechnology (Guangzhou, China).

first: Yue

last: Chen

first: Hao

last: Luo

first: Weihong

last: Lin


title: RNA-seq of human platelets and platelet derived extracellular vesicles (EV)

city: San Francisco

first: Huimin

last: Geng

state: CA

address: 513 Parnassus Ave., MSB HSW 1201

department: Department of Laboratory Medicine

institute: UCSF

summary: To determine the transcriptomic (mRNA and microRNA) content present in  platelets and platelet derived extracellular vesicles (EV) we used RNA-Seq approach. The goal was to determine if the transcriptomic cargo carried by platelet derived extracellular vesicles is different than that of the fresh platelets.

overall_design: Genome-wide profiling of total RNA transcript levels in human Platelet and Platelet derived extracellular vesicles (EV) was performed using RNA Seq

first: Alpa

last: Trivedi

first: Shibani

last: Pati


title: CDC5L in HeLa cell lines

city: Shanghai

first: Shunyi

last: Li

state: Shanghai

address: 100 Haike Rd, Building 13

department: Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry

institute: Chinese Academy of Sciences

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

overall_design: Refer to individual Series


title: Discovery of genes directly bound to CDC5L in HeLa cell lines [ChIP]

summary: We identified the gene cell division cycle 5-like protein (CDC5L), whose knockdown induced SG formation in the absence of any cellular stress. Moreover, lower protein levels of CDC5L  increased mRNA and protein levels of PERK. Through ChIP-PCR, we found that CDC5L regulated transcription by directly binding to PERK promoter.To further clarify the biological function of CDC5L as a transcriptional repressor, we expressed CDC5L-HA in the HeLa cell line, used HA antibodies for chromatin immunoprecipitation, and obtained the promoters to which CDC5L protein directly binds, and performed ChIP-seq analysis.

overall_design: Chormatin immunoprecipitation DNA-seqencing (ChIP-seq) for CDC5L in HeLa cells.

first: Beituo

last: Qian

first: Feng

last: Qiu

first: Yanshan

last: Fang


title: Effects of CDC5L knockdown on gene transcription levels in HeLa cell lines [RNA]

summary: Stress granules (SGs) are membraneless protein condensates that form in the cytoplasm of a cell upon exposure to cellular stressors. Here, we identified the gene cell division cycle 5-like protein (CDC5L), whose knockdown induced SG formation in the absence of any cellular stress. Moreover, lower protein levels of CDC5L increased mRNA and protein levels of PERK. In order to identify  the regulation on the overall cellular transcriptome, especially stress-related genes, after CDC5L knockdown, we used siRNA to knockdown CDC5L and performed RNA-seq in the HeLa cell line.

overall_design:
To invesgate  the specific mechanism of CDC5L in transcriptional repression and its biological function in response to cellular stress, we used siRNA to knock down CDC5L in the HeLa cell line.
We then performed RNA-seq on CDC5L knockdown cells and control cells to compare the effect of CDC5L knockdown on cellular transcription levels.


title: Gene expression profiles of cardiac neural crest cells  during heart development

city: Bunkyo-ku

first: Akiyasu

last: Iwase

state: Tokyo

department: Graduate School of Medicine

country: Japan

institute: The University of Tokyo

summary:
This study aimed to clarify the gene expression of each of cardiac neural crest cells during mouse heart development by using Fluidigm C1 system.  Embryonic hearts from  Wnt1-Cre; R26-EYFP mice, which labeled neural crest cells, at E11.5, E12.5, E14.5 and E17.5 were used for single-cell (sc) RNA-seq.
Citation: Iwase et al., 2026

overall_design: Cells were isolated from outflow tract tissues of the embryonic heart of Wnt1-Cre; R26-EYFP mice at E11.5, E12.5, E14.5 and E17.5 and were sorted into EYFP-positive (neural crest) fractions by the fluorescence activated cell sorting. These cells were subjected to Fluidigm C1 system for  scRNA-seq.

first: Yasunobu

last: Uchijima

first: Daiki

last: Seya

first: Youichiro

last: Wada

first: Hiroki

last: Kurihara


title: Lysyl oxidase (LOX) inhibition creates vulnerability to ferroptosis by disrupting mitochondrial homeostasis in TNBC

status: Public on Jul 19 2026

city: Montreal

first: Morag

last: Park

state: Quebec

address: 1160 Ave des Pins Ouest, Room 514

department: Goodman Cancer Institute

summary: High degree of metabolic heterogeneity and plasticity of triple-negative breast cancer (TNBC) contributes to its aggressiveness and resistance to standard therapies, necessitating identification of novel therapeutic vulnerabilities. Here, we identify previously unrecognized, non-canonical functions of ECM remodeler, lysyl oxidase (LOX), in coupling glucose metabolism with mitophagy and redox homeostasis, and show that inhibiting LOX generates a targetable vulnerability to ferroptosis, an iron-mediated cell death. Mechanistically, LOX directly interacts with PARKIN and its upstream kinase PINK1, which we identified as a novel LOX substrate. LOX-mediated PINK1 oxidation prevents PARKIN phosphorylation, preventing HIF-1α proteasomal degradation, increasing glycolysis. Concomitantly, LOX inhibits PARKIN-mediated mitophagy and triggers mitochondria-ER contacts via preventing VDAC1 proteasomal degradation, while the LOX-HSP90 complex promotes mitochondrial CA2+ transport. Inhibiting LOX disrupts mitochondrial dynamics, reduces OXPHOS and antioxidant GPX4/FSP1, while triggering compensatory DHODH activity in a mitophagy-dependent manner. Our ‘one-two punch’ approach combining LOX inhibitor or shLOX with clinical DHODH inhibitor, leflunomide, leads to strong tumor growth inhibition in multiple in vivo models in a chemo-free setting. Notably, LOX protein correlates with HIF-1α/GLUT1/GPX4 in patient tumors. Together, we present LOX as a therapeutic target, inducing vulnerability to ferroptosis in TNBC.

overall_design: Breast cancer patient-derived xenograft stained with GS6, CD31, and GLUT1. Comparison of Regions of interest (ROI) in areas enriched and not enriched for GLUT1

first: Genevieve

last: Deblois

first: Ozgur

last: Sahin


title: RNA-sequencing analysis of placental tissues from women with and without polycystic ovary syndrome

city: Nanjing

first: Shimin

last: Wu

address: Nanjing

institute: Affiliated Hospital of Nanjing University of Chinese Medicine

summary: This study performed bulk RNA sequencing of term placental tissues collected from women with polycystic ovary syndrome and control pregnancies. The placental transcriptomic analysis was conducted to explore potential molecular alterations associated with the amniotic fluid metabolic changes identified in the accompanying study

overall_design: human placental tissues from women with PCOS and controls


title: Novel Mechanism of Gene Expression Regulation [RNA-Seq]

first: wenjie

last: liang

address: Guoquan North Road

institute: Fudan university

summary: This study describes a novel mechanism by which histones and transcription factors coordinately regulate gene expression in plants.

overall_design: For each genotype, seedlings were divided into two groups: untreated control and Zeocin-treated group to induce DNA damage. Two independent biological replicates (A and B) were generated for every sample. Whole-transcriptome RNA-seq and H3K4me3 ChIP-seq were performed separately. ChIP Input libraries without antibody enrichment were prepared as background controls for ChIP-seq. Paired-end sequencing was applied for all libraries. This dataset compares transcriptional profiles and genome-wide H3K4me3 enrichment patterns across genotypes and damage treatments to investigate coordinated gene regulation by histone modification and transcription factors.


title: Effect of semaglutide treatment in aged mice

city: Berkeley

first: Yufan

last: Feng

address: Morgan hall

institute: University of California, Berkeley

summary: Semaglutide is a GLP-1R agonist. We investigated the effect of semaglutide in aged mice. We treated 20-month-old female C57BL/6 mice with semaglutide for three months and performed RNA-sequencing analysis of liver samples.

overall_design: Bulk RNA-sequencing data from liver samples of aged control mice and semaglutide-treated mice.

first: Marine

last: Barthez

first: Danica

last: Chen


title: Human Blood Exposure to Neutron Radiation at Two Irradiation Facilities

city: Kingston

first: Michael

last: Antosh

state: RI

address: 2 Lippitt Rd

institute: University of Rhode Island

summary: Human blood from 12 donors was exposed to increasing doses of neutron radiation at two sites: the Rhode Island Nuclear Science Center (RINSC), and the Radiological Research Accelerator Facility (RARAF) at Columbia University. The exposure at the Rhode Island Nuclear Science Center was largely thermal neutrons, and the exposure at the Radiological Research Accelerator Facility was largely fast neutrons. Samples were measured for RNASeq differential expression.

overall_design: 120 total samples. 12 human blood donors, 10 samples per donor. For each donor, the 10 samples were 2 exposure sites (RINSC, RARAF) times 5 doses: 0, 0.5, 1.0, 2.0, and 4.0 Gy.

first: Sally

last: Amundson


title: Novel Mechanism of Gene Expression Regulation


title: Integrated Sensing of Viral RNA and RNase L-Driven Intron Retention Orchestrates Anti-Poxvirus Immunity

city: Nashville

first: John

last: Karijolich

state: TN

address: 1211 Medical Center Drive

department: PMI

institute: Vanderbilt University Medical Center

summary: The recognition of double-stranded RNA (dsRNA) is a critical component of antiviral innate immune responses, yet how distinct sensors integrate their activities to enforce restriction remains unclear. Here, we uncover a cooperative mechanism linking the OAS3-RNase L and PKR pathways during vaccinia virus (VacV) infection. Transcriptome-wide analyses reveal that RNase L activation disrupts pre-mRNA splicing, inducing widespread intron retention. These retained introns form dsRNA structures that evade nuclear quality control, accumulate in the cytoplasm, and serve as ligands for PKR. Thus, RNase L reshapes the transcriptome to enhance the generation of immunostimulatory substrates, amplifying PKR activation. In parallel, we identify conserved viral RNAs derived from the VacV telomeres, whose terminal loop architectures directly modulate PKR activity, with distinct species either promoting or dampening its activation. Together, our findings establish that PKR signaling emerges from the integrated detection of host-derived introns and conserved viral terminal structures, revealing innate immune cooperativity at the interface of RNA processing, viral replication, and gene regulation.

overall_design:
1. RNA-seq profiling of uninfected A549 cells and A549 cells infected with VacV (Western Reserve strain) and VacV_dE3L (E3L deletion mutant, Western Reserve strain) at MOI of 1 for 6 hours and 24 hours, respectively.
2. RNA immunoprecipitation-sequencing (RIPseq) using J2 antibody for the profiling of dsRNAs in uninfected A549 cells and A549 cells infected for 24 hours with VacV (Western Reserve strain) and VacV_dE3L (E3L deletion mutant, Western Reserve strain) at MOI of 1, respectively.
3. Formaldehyde crosslinking RNA immunoprecipitation-sequencing (fRIPseq) for the profiling of PKR bound-RNAs in uninfected A549 cells and A549 cells infected for 24 hours with VacV (Western Reserve strain) and VacV_dE3L (E3L deletion mutant, Western Reserve strain) at MOI of 1, respectively.

first: Ruilin

last: Zhang

first: Xiang

last: Ye

first: Andrew

last: Dixson

first: Yang

last: Zhao

first: Alissa

last: Weaver


title: A Phospho-Regulatory Switch Governs the Timing of Cortical Development

city: Odense M

first: Xuan

last: Wang

address: Munkebjergvænget 14, Thriges Kollegium Edison A

department: IMM

country: Denmark

institute: University of Southern Denmark

summary: The development of the cerebral cortex requires precise temporal control of transcription factor (TF) activity, yet how this is achieved remains unclear. Here we employ a comprehensive multi-omics approach during murine cortical development, integrating proteomic and phosphoproteomic analyses with chromatin accessibility and gene expression profiling to uncover novel Phospho-switches driving cortical cell-fate transitions. Our findings reveal distinct phosphorylation dynamics of several TFs that correlate with their developmental-stage and cell-type-specific activity. Among these, we reveal a functional handoff between two TFs: Hmgn3, a "progenitor keeper," and Nfib, a "neuronal maturation driver” during early cortical development. Site-specific phosphorylation acts as a functional rheostat; phosphorylation at S78 on Hmgn3 influences progenitor proliferation, while phosphorylation at S265 on Nfib is essential for neuronal maturation. Mechanistically, we demonstrate that S265 phosphorylation is a genomic targeting signal that directs Nfib to distal enhancers of key developmental genes. Crucially, residues proximal to the Nfib S265 phosphosite are hotspot for variants in human neurodevelopmental disorders.   Our findings establish a model where phosphorylation dictates TF activity to control developmental timing and balance the excitatory and inhibitory neurons at early time points and the glial cell population at later stages, providing critical insights into human brain development and disease. This integrated analysis enhances our understanding of the molecular foundations of cortical development and highlights the critical role of phosphorylation in regulating TF activity in a stage- and cell-type-specific manner to govern cellular diversity.

overall_design: Plugged C57BL/6J females were purchased from Janvier Labs and E0.5 was defined as the morning on which the vaginal plug appeared. Mice were subjected to in utero electroporation and embryos harvested as previously described41. Electroporation was performed using the pCAG-mScarlet-3XFlag vector encoding for Nfib-WT, Nfib-S265A, Hmgn3-WT, Hmgn3-S78A, and an empty vector served as a control. In brief, plasmids were prepped using an NncleoBond Xtra Maxi Endotoxin-free Plasmid maxi kit (Cat no: 740424.10) and plasmid concentration adjusted to 1.5 μg/μl. Pregnant mice were anaesthetised with isofluorane at E13.5 and ∼1.5 μl of plasmid solution was injected into the ventricle of embryonic brains. The plasmids were electroporated into the dorsal ventricular zone with six pulses of 30 V, 50 ms each at 1 s interval delivered through platinum electrodes using round electrodes CUY650P5 and Nepa Gene electroporator (NEPA21 Type II). After four days of electrophoration (E17.5), the brain tissues were processed for the analyses. For the isolation of electroporated cells from E17.5, the dorsolateral neocortex was dissected, and a single cell suspension was produced from two to three hemispheres per condition using the MACS Neural Tissue Dissociation kit containing papain (Miltenyi Biotec, 130-092-628). The cells were resuspended to 1 million cells/ml in FACS buffer (3%BSA, 1mM EDTA in HBSS w/o Ca2+ and Mg2+), passed through a 40-μm filter and immediately processed by FACS on a five-laser Invitrogen BIGFOOT cell sorter. For each condition, 30,000 to 100,000 cells were collected in 1.5 mL DNA LoBind tubes containing FACS buffer. scRNA-seq libraries were generated according to Parse Biosciences protocols: Evercode Cell Fixation v3 and Evercode WT Mini v3. For cell fixation, FACS sorted single cell suspensions were centrifuged for 10 min at 200g at 4°C in 15-ml BSA-coated Falcon tubes and resuspended in Cell Prefixation Buffer with BSA 7.5% (Gibco) in 15-ml BSA-coated Falcon tubes. Cell suspensions were incubated in fixation solution followed by the addition of permeabilization solution and stop buffer, according to the manufacturer’s instructions. Cell suspensions were frozen using a Mr. Frosty Freezing container (Sigma-Aldrich) at −80°C until further use. Samples barcoding and sub-libraries were prepared using the Evercode WT Mini v3 as per the manufacturer's instructions and sequenced on a NovaSeq 6000 instrument. CUT&RUN experiments were performed on E17.5 IUE sorted cells using specific antibodies for the following proteins: Flag (Sigma, M2 clone F1804), and normal IgG. Biological replicates were generated for all the CUT&RUN assays. Samples were prepared following the EpiCypher CUTANA ChIP/CUT&RUN Kit protocol (Epicypher, SKU: 14-1048). An IgG antibody served as a negative control to evaluate non-specific background signal from chromatin captured during immunoprecipitation, and an E. Coli spike-in control was added for normalizing enrichment during analysis. CUT&RUN libraries were prepared according to the CUTANA™ CUT&RUN Library Prep Kit (Epicypher) for Illumina, and each sample was uniquely barcoded with the Multiplex Oligos for Illumina. Libraries were pooled and sequenced using 75 base pair paired-end reads on the NovaSeq 6000 platform, obtaining a sequencing depth of at least 10 million reads per sample.

first: Arun

last: Mahesh

first: Anuj

middle: K

last: Dwiwedi

first: Souren

last: Sadhukhan

first: Vijay

last: Tiwari


title: A Phospho-Regulatory Switch Governs the Timing of Cortical Development [scRNA]

overall_design: Plugged C57BL/6J females were purchased from Janvier Labs and E0.5 was defined as the morning on which the vaginal plug appeared. Mice were subjected to in utero electroporation and embryos harvested as previously described41. Electroporation was performed using the pCAG-mScarlet-3XFlag vector encoding for Nfib-WT, Nfib-S265A, Hmgn3-WT, Hmgn3-S78A, and an empty vector served as a control. In brief, plasmids were prepped using an NncleoBond Xtra Maxi Endotoxin-free Plasmid maxi kit (Cat no: 740424.10) and plasmid concentration adjusted to 1.5 μg/μl. Pregnant mice were anaesthetised with isofluorane at E13.5 and ∼1.5 μl of plasmid solution was injected into the ventricle of embryonic brains. The plasmids were electroporated into the dorsal ventricular zone with six pulses of 30 V, 50 ms each at 1 s interval delivered through platinum electrodes using round electrodes CUY650P5 and Nepa Gene electroporator (NEPA21 Type II). After four days of electrophoration (E17.5), the brain tissues were processed for the analyses. For the isolation of electroporated cells from E17.5, the dorsolateral neocortex was dissected, and a single cell suspension was produced from two to three hemispheres per condition using the MACS Neural Tissue Dissociation kit containing papain (Miltenyi Biotec, 130-092-628). The cells were resuspended to 1 million cells/ml in FACS buffer (3%BSA, 1mM EDTA in HBSS w/o Ca2+ and Mg2+), passed through a 40-μm filter and immediately processed by FACS on a five-laser Invitrogen BIGFOOT cell sorter. For each condition, 30,000 to 100,000 cells were collected in 1.5 mL DNA LoBind tubes containing FACS buffer. scRNA-seq libraries were generated according to Parse Biosciences protocols: Evercode Cell Fixation v3 and Evercode WT Mini v3. For cell fixation, FACS sorted single cell suspensions were centrifuged for 10 min at 200g at 4°C in 15-ml BSA-coated Falcon tubes and resuspended in Cell Prefixation Buffer with BSA 7.5% (Gibco) in 15-ml BSA-coated Falcon tubes. Cell suspensions were incubated in fixation solution followed by the addition of permeabilization solution and stop buffer, according to the manufacturer’s instructions. Cell suspensions were frozen using a Mr. Frosty Freezing container (Sigma-Aldrich) at −80°C until further use. Samples barcoding and sub-libraries were prepared using the Evercode WT Mini v3 as per the manufacturer's instructions and sequenced on a NovaSeq 6000 instrument.


title: CnbHLH130 positively regulates salt tolerance through CnCBL10-CnCIPK4 mediated SOS pathway in Campeiostachys nutans [RNA-Seq_BSMV]

city: Yangling

first: Juanjuan

last: Fu

state: Shaanxi

address: No.22 Xinong Road

institute: Northwest A&F University

summary: Campeiostachys nutans, a dominant perennial grass in the Qinghai-Tibet Plateau, exhibits high tolerance to salt stress. The Salt Overly Sensitive (SOS) pathway is key to plant salt stress tolerance. However, the pivotal role of the SOS pathway in response to salt stress in C. nutans remains unknown. Here, we identified CnbHLH130 as a novel transcriptional activator of CnCBL10, directly binds to the G-box motif in the promoter. CnbHLH130 responds to salt stress and positively regulate salt tolerance in rice and C. nutans. Interestingly, we found CnCBL10 and CnCIPK4 interact with CnbHLH130 by a Y2H screening assay. The interactions were confirmed by split-luciferase complementation (split-LUC), Pull-down, Co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays. Moreover, CnbHLH130 enhanced the interaction between CnCBL10 and CnCIPK4, which further phosphorylate and activate Na+/H+ antiporter CnSOS1 to exclude excess cytosolic Na+ from cells in the shoots. Genetic evidence showed that CnCBL10, CnCIPK4 and CnbHLH130 coordinately regulates salt tolerance in plants. In summary, this study demonstrated that CnbHLH130 acts as a novel core component and transcriptional activator regulating CnCBL10-CnCIPK4 mediated SOS pathway, thus conferring to the salt tolerance in C. nutans. This work advanced our understandings of how an alpine plant greatly survived in the Qinghai-Tibet Plateau by concise regulation of the SOS pathway in response to salt stress.

overall_design: Barley stripe mosaic virus (BSMV)-mediated gene silencing was performed in leaves of 4-week-old Campeiostachys nutans seedlings.  Seedlings infected with BSMV:γ  served as a control. After 10 days post-incubation, the BSMV:γ  and BSMV:CnbHLH130 seedlings were grown under normal conditions and subjected to salt treatment (200 mM NaCl for 5 days). Briefly, this experiment include two genetypes (BSMV:r, non-silenced control and BSMV:CnbHLH130, CnbHLH130-silenced line), which were divided into two groups, one group for salt stress treatment (S_BSMV_r; S_BSMV_CnbHLH130) and another group for without salt treatment (BSMV_r; BSMV_CnbHLH130).


title: Genetic regulation of tRNA and its trans effect on genetic disease

city: Hangzhou

first: Ke

last: Ding

address: No. 1369, West Wenyi Road

institute: Zhejiang university

type: Non-coding RNA profiling by high throughput sequencing

summary: In this study, we predicted multiple tRNA regulators based on large-scale smRNA-seq data and identified several potential regulators, including ZNF460 and MEF2C. To further validate the functions of these potential regulators, we generated knockout strains for each gene in HEK293T cells using two independent shRNAs (biological replicates), each with three technical replicates. We then performed small RNA-seq experiments after nuclear extraction to measure transcriptome-wide differences in tRNA abundance.

overall_design: To validate the candidate regulators, we performed knockdown experiments in human HEK293T cells, which were cultured in DMEM supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin, maintained at 37 °C with 5% CO2. shRNAs targeting MEF2C and ZNF460 were cloned into the pLKO.1 vector (Sigma-Aldrich), with all shRNA sequences listed in Supplementary Table. Total RNA was extracted using TRIzol reagent and reverse-transcribed with the HiScript II 1st Strand cDNA Synthesis Kit, followed by qPCR using SYBR Green Master Mix with GAPDH as the internal control. Primer sequences are also provided in the supplementary table. For smRNA sequencing, libraries were prepared using the NEB Next Small RNA Library Kit with 1 µg of total RNA per sample. Two shRNAs with similar knockdown efficiency were used for each gene, with three biological replicates. Sequencing was conducted on the NovaSeq X Plus platform with PE150 single-indexed reads, yielding 10 million reads per sample for PAGE-purified libraries and 15 million reads for libraries purified by dual-round magnetic bead selection. Due to read-through during sequencing, we observed the presence of long polyG and polyT stretches at the 3' ends of the reads. To mitigate this artifact, we trimmed the last 100 bp of each read using cutadapt before proceeding with alignment and quantification.

first: Jiuhong

first: Yi

first: Xushen

last: Xiong


title: The subcoeruleus nucleus mediates specific immune response in the lungs via sympathetic nerve

first: Xiaoyu

last: Sun

address: 160 Pujian Road, Shanghai

institute: Renji Hospital, Shanghai Jiaotong University, School of Medicine,

summary: In this study, single-cell RNA sequencing (scRNA-seq) was conducted on lung tissues from adult C57BL/6J male mice under various experimental conditions. The mice were divided into control, LPS-treated, and SLC-Gq activation + LPS groups. Lung tissues were collected three days after intratracheal administration of PBS or LPS. Single-cell suspensions were prepared and processed using the BD Rhapsody system for scRNA-seq. Our objective was to investigate cell type-specific responses and transcriptional profiles in the lung microenvironment following LPS challenge, with or without SLC activation. The results provide a comprehensive single-cell atlas of mouse lung immune responses and potential targets for future interventions.

overall_design: Male C57BL/6J mice (12 weeks) were randomly assigned to (1) control (PBS), (2) LPS (1 mg/kg), or (3) SLC-Gq activation + LPS groups, with two biological replicates per group. Three days after treatment, lung tissues were collected, and single-cell suspensions were generated via enzymatic digestion. Single-cell RNA-seq libraries were constructed using the BD Rhapsody protocol and sequenced on the DNBSEQ-T7 platform (BGI). Library quality was assessed with Bioanalyzer and Qubit. Downstream analysis focused on cell-type identification, differential gene expression, and immune landscape characterization.

first: Wanbing

last: Dai

first: Qiang

first: Sihan

last: Chen


title: Single-Cell Multiomic Profiling of the Mouse Hippocampus During Ageing and Memory Formation

city: London

first: Paul

last: Lavender

address: Guy's Hospital, Great Maze Pond

institute: King's College London

summary: The exact epigenetic changes underlying memory formation in the hippocampus, and how this changes with age, remain unclear. To investigate this, we profiled the hippocampi of young and old mice in naive states and 3hr after contextual fear conditioning.

overall_design: Single-nuclei were isolated from the hippocampi of young and old mice in naive states and 3hr after contextual fear conditioning. Joint snRNA- and snATAC-seq libraries were prepared using the 10x Genomics Platform.

first: Andrew

middle: C

last: Graham

first: Albert

last: Basson


title: Profile of innate immunity in the skin of patients with SARS-CoV-2

city: São Paulo

first: Maria

middle: Notomi

last: Sato

state: São Paulo

address: Av. Dr. Eneas de Carvalho Aguia, 470

department: Dermatology

country: Brazil

institute: University of São Paulo

summary: The proposal is to analyse global immunity genes in the RNA sequencing of the skin of patients with SARS-CoV-2 We analyzed 8 samples of skin samples from post-mortem patients from Covid-19 of Hospital das Clinicas da Faculdade de Medicina da USP de Sao Paulo. To compare we used 5 skin biopsy from healthy controls, submitted to plastic surgery.

overall_design: Skin samples were obtained from autopsies of COVID-19 patients, as well as from healthy control individuals undergoing plastic surgery, for RNA sequencing.

first: Iara

last: Fernandes

first: Frederico

last: Ferreira

first: Emanuella

last: Souza

first: Anna

middle: J

last: Pietrobon

first: Yasmim

last: Ramos

first: Mirian

last: Sotto

first: Amaro

last: Duarte Neto

first: Emily

last: Oliveira

first: Luiz

middle: F

last: Silva


title: Nanodrug modified with engineered cancer cell membrane targets CDKs to activate PD-L1 antibody immunotherapy against liver metastasis of immune-desert colon cancer

city: Guangzhou

first: Dongbing

last: Ding

address: 600 Tianhe Road, Tianhe District, Guangzhou City, Guangdong Province

institute: The Third Affiliated Hospital of Sun Yat-sen University

summary: Immunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the MSS/pMMR subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Thus, turning the tumor microenvironment immunologically hot is critical for activating a potent immunotherapy through immune checkpoint blockade (ICB) in this unique subtype accounting for 85% cases of total colon cancer. Here, a multifunctional nanodrug (NP-D@MP) carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody to boost the ICB-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modified the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. The nanodrug boosted the immunogenicity of tumor microenvironment, thus improving response rate of PD-L1 antibody treatment. First, CDK inhibitor (CDKi) delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells (TAMCs) sensitizing ICB therapy in CCLM of murine CT26 cell. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft (PDX) model and the patient-derived organoid (PDO) model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the TIME, and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.

overall_design: To investigate the role of current biomimicking nanodrugs to colon cancer, the total RNA of CT26 cells treated with PBS, NP@M, NP-D@M, and NP-D@MP for 24 h was extracted for RNA seq.

first: Rongpu

last: Liang

first: Tan

last: Li

first: Tianyun

last: Lan


title: Boldine treatment prevents chronic cognitive impairment and exaggerated fear learning in rats exposed to repetitive low-level blast injury

status: Public on Jul 18 2026

city: Bronx

first: Alexey

last: Kozlenkov

address: 130 W Kingsbridge Road

institute: Icahn School of Medicine at Mount Sinai

summary: Many Veterans who experienced blast-related traumatic brain injuries (TBI) during their military service suffer from chronic cognitive and mental health problems including post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast injuries designed to mimic the type of blast-related mild TBI that was so common in the conflicts in Iraq and Afghanistan conflicts develop delayed and persistent cognitive and PTSD-related traits that remain present for over one year after exposure. Boldine, an alkaloid derived from the Chilean Boldo tree (Peumus boldus), is widely used herbal remedy with anti-oxidant, anti-inflammatory, hepatoprotective, and connexin hemichannel-blocking properties. We studied whether oral administration of boldine could prevent development of PTSD-related behavioral traits in rats exposed to repetitive low-level blast. Treatment with boldine prevented appearance of the blast-induced PTSD-like phenotype including object recognition deficits and exaggerated cued fear learning. Boldine also prevented blast-induced elevation of the metabotropic glutamate receptor (mGluR2) and the N-methyl-D-aspartate receptor 2b (NMDAR2b), but did not reverse decreases in the serotonin 5-HT2A receptor. Representative IbaI immunofluorescence images suggested that Boldine reduced blast-associated microglial process retraction in sensimotor cortex; quantitative morphometric analysis supports this conclusion. Bulk hippocampal RNA-seq did not identify individual genes that remained significant after FDR correction. Exploratory analysis of 85 nominally significant candidates suggested that boldine is associated with coordinated transcriptional changes related to cognition and neurotransmitter transport, consistent with modulation of activity-regulated transcription factors and neuroimmune signaling. These studies suggest that boldine may be beneficial for the neurobehavioral syndromes that follow blast exposure in military Veterans, while highlighting the need for validation in both sexes and in treatment paradigms initiated after symptoms have emerged.

overall_design: Bulk RNA and RNA-seq libraries were prepared from bulk brain tissue of 6 boldine-treated and 6 untreated blast-exposed rats.

first: Christopher

last: Cardozo

first: Carlos

last: Toro


title: Cell type alternation at single cell level of the germ-free mice colon colonized with BT strains

first: Zhongle

last: Cai

address: No.573, Xujiahui Road, Huangpu District, Shanghai

institute: ruijin hospital

summary: Intestinal epithelium is the direct interface between host and microbes and responds to the microbial metabolites. We used single cell RNA sequencing (scRNA-seq) to analyze the alternation of epithelial cell types in the colons from germ-free mice colonized with BT strains

overall_design: Intestinal cells of the germ-free mice, germ-free mice colonized with BT strains were isolated from the colon tissue and analyzed using scRNAseq.

first: Xingyu

last: Wang

first: Yingkai

last: Sun

first: Ruinxin

last: Liu


title: Patient Derived Neomorphic SEPTIN6 Mutations Induce Hematopoietic Stem Cell Senescence Underlying Congenital Neutropenia and Myelodysplasia

city: Boston

first: Safa

last: Mohamad

state: MA

address: 125 Park Drive, Apt 15

institute: Boston Children's Hospital/ Harvard Medical School

summary: Septins are RAS-like GTP-binding proteins involved in cytoskeletal organization and cellular division. We previously described two pediatric patients harboring SEPT6 germline mutations (GM1:SEPT6 c.1282T>C and GM2:SEPT6 c.1282T>A) presenting with congenital neutropenia associated with the development of myelodysplastic syndrome. In one patient, an additional somatic mutation (SM:SEPT6 c.43C>T) was detected at a low allelic fraction in the BM. Here, we describe the consequences of these mutations on hematopoiesis. Transgenic expression or gene editing of GM1 or GM2 in human CD34+ cells led to enlarged, multinucleated cells associated with accelerated exhaustion and premature senescence of hematopoietic stem and progenitor cells (HSPCs). Senescence defects were associated with the upregulation of mTOR phosphorylation; and pharmacologic inhibition of the mTOR pathway resulted in rescue of senescence. In parallel, HSPCs exhibited marked mitochondrial abnormalities, including increased expression of OPA1, a key regulator of mitochondrial fusion, and enhanced oxygen consumption during mitochondrial respiration. Introduction of SM in cis with GM1 mitigated all observed defects. Collectively, our findings demonstrate a gain-of-function mechanism underlying marrow failure in patients carrying germline SEPT6 mutations and suggest that acquisition of a secondary somatic SEPT6 variant may confer a compensatory effect within hematopoietic cells.

overall_design: Human CD34+ cells were transduced using a lentivirus into the following four groups: 1. EV control, 2. SEPT6 shmiR+ WT SEPT6, 3. SEPT6 shmiR+GM1 and 4. SEPT6 shmiR +GM1+SM. The four groups were cultured for 5 days as described above. On day 5 cells were sorted into GFP+CD34+CD45RA- fraction and submitted to the Translational Immunogenomics Lab (TIGL) at the Dana Farber Institute for further single cell mRNA sequencing analysis.

first: Yu

last: Zhou

first: David

last: Williams


title: Functional dissection of enhancers in 2-Cell embryo with an in vitro model.

first: Man

last: Zhang

state: Guangdong

address: No.9, XingDaoHuanBei Road, Guangzhou International Bio-island, Haizhu District

department: Department of Basic Research

institute: Guangzhou Laboratory

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

overall_design: Refer to individual Series


title: Transcriptomic changes in the mouse olfactory bulb following peripheral SARS-CoV-2 infection

city: Iowa City

first: Stanley

last: Perlman

state: Iowa

address: 51 Newton Road

department: Dept of Microbiology and Immunology

institute: University of Iowa

summary: Neuroinflammation and microglial activation in the olfactory bulb have been reported in animal models of SARS-CoV-2 infection. This study aims to characterize the neuronal transcriptional changes associated with these neuroinflammatory responses.

overall_design: Middle-aged B6 mice were infected with SARS2-N501YMA30 (1000 PFU/mouse). Olfactory bulbs were collected in TRIzol from mock-infected mice and infected mice at 6 and 30 days post-infection (dpi). Total RNA was extracted from these samples and submitted for RNA sequencing.

first: Abhishek

last: Verma

first: Lu

last: Tan


title: Benchmarking CUT&RUN analysis procedure using motif enrichment

city: Toronto

first: Luomeng

state: Ontario

address: 101 College St

institute: University of Toronto

summary: We designed a benchmarking method to evaluate peak calling procedures for CUT&RUN data and the effects of varying preprocessing approaches, such as fragment length filtering and spike-in calibration. To support this work, we generated new CUT&RUN datasets with distinct experimental characteristics alongside publicly available datasets. In particular, we produced libraries with an average read length of approximately 133 bp—longer than typical CUT&RUN read lengths—which provide higher sequencing coverage and improved read mappability. These datasets provide complementary data for evaluating how experimental characteristics influence preprocessing strategies and peak-calling performance in CUT&RUN.

overall_design: We employed CUT&RUN across transcription factor samples (CEBPB and ZNF143) in K562 cells. We also included corresponding IgG control.

first: Coby

last: Viner

first: Xing Hao

first: Michael

last: Wrana

first: Charles

last: Ishak

first: Shu Yi

last: Shen

first: Daniel

middle: D

last: De Carvalho

first: Sarah

last: Hainer

last: Hoffman


title: Identification of the Molecular Targets Underlying the Anticancer Effects of Betulonic Acid, One of the Active Constituents of Celastrus orbiculatus, in Gastric Cancer Cells

city: Shanghai

first: Zewen

last: Chu

address: 1200 Cai Lun Road

institute: Shanghai University of Traditional Chinese Medicine

summary: To investigate the potential targets, related signaling pathways, and molecular mechanisms of betulonic acid, one of the active constituents of Celastrus orbiculatus, in gastric cancer cells, reference-based transcriptome sequencing was performed.

overall_design: In two gastric cancer cell lines, AGS and HGC-27, betulonic acid was administered, and reference-based transcriptome sequencing was performed to compare the treated groups with the untreated control groups.

first: Yue

last: Ding

first: Yanwei

last: Xiang


title: Mapping genetic modifiers of epimutation rates identifies VIM2/4 as dosage-sensitive negative regulators of CG methylation maintenance [WGBS_VIM2/4]

city: Freising

first: Zhilin

state: Bavaria

address: Emil-Ramann-Str. 4

department: School of Life Sciences

country: Germany

institute: Technical University of Munich

summary: Spontaneous epimutations are stochastic gains and losses of cytosine methylation that arise from imperfect maintenance across cell divisions. At CG sites, such epimutations can be inherited across generations in plants and constitute a major source of CG methylation (mCG) diversity. However, why the fidelity of mCG inheritance varies among genotypes, and how this variation relates to steady-state mCG levels, remain poorly understood. Here we tracked DNA methylation over ten generations in ~400 mutation-accumulation lines derived from ~70 Arabidopsis thaliana Ler × Cvi recombinant inbred founders. By treating methylation gain and loss rates as quantitative molecular traits, we mapped a major-effect locus to a Cvi-derived deletion between VIM2 and VIM4, two components of the MET1-dependent mCG maintenance pathway. Lines carrying this deletion showed elevated VIM2/4 expression, a rapid shift of genome-wide mCG toward a lower steady state, and reduced fidelity of methylation inheritance across generations. Complementary overexpression and loss-of-function experiments identify VIM2 and VIM4 as dosage-sensitive negative regulators of mCG maintenance, in contrast to the canonical positive role of VIM-family proteins in CG methylation. Together, our results support a punctuated-equilibrium model of DNA methylome evolution, in which naturally segregating modifiers of mCG homeostasis can produce abrupt shifts in methylation state and alter the rate at which heritable epigenetic variation accumulates in plant genomes.

overall_design: We generated independent VIM2/4 overexpression lines and VIM2 and VIM4 single mutants. Transgenic lines overexpressing VIM2, VIM4, or both paralogues (VIM24) were generated in the Col-0 background using Col-0 or Cvi-0 alleles.

first: Wilma

last: Wanney

first: Frank

last: Johannes


title: Mapping genetic modifiers of epimutation rates identifies VIM2/4 as dosage-sensitive negative regulators of CG methylation maintenance [RNAseq_VIM2/4]

overall_design: RNA-seq was performed to profile transcriptional changes associated with VIM2/4 dosage perturbation and natural variation in epimutation rates. The dataset includes Col-0 wild-type controls, vim2 and vim4 loss-of-function mutants, VIM2, VIM4, and VIM2/4 overexpression lines in the Col-0 background (using Col and Cvi alleles), and Ler x Cvi recombinant inbred lines (RILs) selected for high or low epimutation rates at generations 3 and 10.

first: Yangyang

last: Xu

first: Robert

last: Schmitz


title: Cystine Restriction Alleviates T Cell Exhaustion and Enhances CAR-T Cell Potency

city: Beijing

first: Haopeng

last: Hong

address: Xicheng street

institute: Peking University First Hospital

summary: This study was designed to explore how targeting Slc7a11 affected CD8+ T cell differentiation and function using a mouse colorectal cancer model. TCR-seq was used to profile T cell receptor repertoires in mouse tumor-infiltrating T cells from wild-type and Slc7a11 knockout tumor models treated with IgG control or anti-Ctla4 antibody.

overall_design: TCR-seq libraries were generated from mouse tumor-infiltrating T cells from four experimental groups: Wt + IgG, Wt + anti-Ctla4, Slc7a11 knockout + IgG, and Slc7a11 knockout + anti-Ctla4. Each GEO Sample contains one Cell Ranger library represented by two paired-end sequencing runs.


summary: This study was designed to explore how targeting Slc7a11 affected CD8+ T cell differentiation and function using a mouse colorectal cancer model. Single-cell RNA-seq was used to monitor tumor-infiltrating CD8+ T cells from Slc7a11 knockout and wild-type mouse tumor models treated with IgG control or anti-Ctla4 antibody.

overall_design: 10x Genomics single-cell RNA-seq of mouse tumor-infiltrating CD8+ T cells from four experimental groups: Wt + IgG, Wt + anti-Ctla4, Slc7a11 knockout + IgG, and Slc7a11 knockout + anti-Ctla4. Each GEO Sample contains one Cell Ranger library represented by two paired-end sequencing runs.


title: Systematic multivariate analysis of chromatin complex dependencies reveals Set1C/COMPASS as a melanoma-enriched epigenetic vulnerability

city: Charlottesville

first: Mohammad

last: Fallahi-Sichani

state: Virginia

address: Box 800759, Health System

department: Biomedical Engineering

institute: University of Virginia

summary: Melanoma exhibits lineage-specific transcriptional programs that may create selective epigenetic vulnerabilities. To identify melanoma-enriched chromatin dependencies, we analyzed large-scale CRISPR gene-dependency data from cancer cell lines together with curated epigenetic complex annotations. This analysis identified the H3K4 methyltransferase complex Set1C/COMPASS as a melanoma-enriched dependency, with CXXC1 emerging as a selectively required subunit in a subset of melanoma cell lines. Functional validation using iterative indirect immunofluorescence imaging (4i) and quantitative single-cell analysis showed that siRNA-mediated depletion of CXXC1 reduced global H3K4me3 levels and impaired proliferation in CXXC1-dependent melanoma cell lines. To define the transcriptional consequences of Set1C/COMPASS perturbation, we performed bulk RNA sequencing (RNA-seq) following siRNA-mediated depletion of CXXC1. Four melanoma cell lines (UACC62, LOXIMVI, MALME3M, and SKMEL28) were transfected with siCXXC1 or a non-targeting control (siNTC), with three independent biological replicates per condition. RNA was harvested 96 hours post-transfection and sequenced to quantify genome-wide expression changes associated with CXXC1 depletion. Transcriptomic analysis revealed suppression of proliferation-associated gene expression programs, including MYC and E2F target signatures, in CXXC1-dependent melanoma cell lines.

overall_design: Four human melanoma cell lines (UACC62, LOXIMVI, MALME3M, and SKMEL28) were transfected with siRNA targeting CXXC1 or a non-targeting control (siNTC) and subjected to bulk RNA sequencing 96 hours post-transfection.

first: Luisa

middle: Q

last: Camacho


title: SRF fusion oncogenes encode constitutively activated chimeric transcription factors in myoid soft tissue tumors [C2C12]

city: Brussels

first: Jean-Baptiste

last: Demoulin

address: av Hippocrate 75, B1.74.05

department: de Duve Institute

country: Belgium

institute: Université catholique de Louvain

summary: SRF fusion genes result from chromosomal translocations in muscle-related soft tissue tumors, including perivascular tumors, myofibroma and rhabdomyosarcoma. SRF encodes the Serum Response Factor, a well-characterized transcription factor that dimerizes and associates with the cofactors TCF or MRTF to regulate muscle development. Here, we characterized four SRF fusion genes: SRF::RELA, SRF::FOXO1, SRF::ICA1L and SRF::PDGFRB. All fusions proteins were nuclear and dimerized through the SRF MADS box.  SRF::RELA, SRF::FOXO1, and SRF::ICA1L acted as constitutively active transcription factors, independently of canonical cofactors. Their activity depended on the DNA-binding MADS box of SRF and the transactivation domain of the partner protein. We identified a cryptic transactivation domain within cytosolic ICA1L. These three SRF fusions promoted mesenchymal cell proliferation and upregulated muscle-related genes. They are representative of 98% of the identified SRF fusion cases. In contrast, SRF::PDGFRB activity relied on the tyrosine kinase domain and was sensitive to imatinib. SRF::PDGFRB acted as an oncogene in Ba/F3 cells, activated STAT1 signaling, and induced an interferon-like inflammatory response, in line with the inflammatory myofibroblastic tumor, in which that fusion was identified. In conclusion, SRF fusions constitute a novel family of oncogenes supporting cell proliferation and expression of muscle differentiation markers in myoid soft tissue tumors.

overall_design: RNA-sequencing on C2C12 lines expressing pMSCV, SRF, SRF-FOXO1, SRF-ICA1L, SRF-RELA and SRF-PDGFRB and comparison of the conditions

first: Pirson

last: Constance

first: Sablon

last: Ariane

first: Loriot

last: Axelle

first: Demoulin

last: Jean-Baptiste


title: SRF fusion oncogenes encode constitutively activated chimeric transcription factors in myoid soft tissue tumors [MSC_hTERT]

overall_design: RNA-sequencing on MSC_hTERT lines expressing pMSCV, SRF, SRF-FOXO1, SRF-ICA1L, SRF-RELA and SRF-PDGFRB and comparison of the conditions


title: Expression data from human dermal papilla cells

city: Mitaka-shi

first: Reina

last: Hayakawa

address: Shinkawa 6-20-2

department: Department of dermatology

institute: Kyorin university faculty of medicine

summary:
Dermal papilla is pivotal for hair follicle morphogenesis and regeneration. However, isolation of human DP cells still depends on laborious microdissection and in vitro expansion impairing their hair-inductive capacities.
We established a novel culture condition maintaining human DP cell properties and analyze global gene expression profiles between DP cells cultured in newly-invented and conventional conditions.

overall_design: DP cells cultured in newly-invented and conventional conditions were used for RNA extraction and hybridization on Affymetrix microarrays. Samples are dermal papilla cells cultured in 10%FBS-DMEM (control), dermal papilla cells cultured with dermal papilla activation culture condition (DPAC), and dermal papilla cells cultured with CHIR99021 added to control (CHIR), dermal papilla cells cultured with recombinant FGF9 added to control (F9) and dermal papilla cells cultured with CHIR99021 and recombinant FGF9 added to control (CHIR+F9).

first: Ryo

last: Takahashi

first: Masahiro

last: Fukuyama

first: Aki

last: Tsukashima

first: Momoko

last: Kimishima

first: Yoshimi

last: Yamazaki

first: Manabu

last: Ohyama


title: Targeting DDR2 for Treating Pancreatic Cancer

city: San Antonio

first: Hanzhou

last: Wang

state: TX

address: 8403 Floyd Curl Drive, MSC 7784

institute: UT Health at San Antonio

summary: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with limited effective treatments, partly due to its complex tumor microenvironment. Herein, we report Discoidin Domain Receptor 2 (DDR2), a receptor tyrosine kinase, as a critical protein that promotes PDAC growth and survival. Our results reveal that DDR2 is highly expressed, and its expression correlates with the worst survival outcome of PDAC patients. Using an unbiased high throughput screen of small molecule inhibitor libraries, we identified CIDD-8633, a novel inhibitor targeting DDR2. Our study suggests that CIDD-8633 interacts with DDR2 and inhibits DDR2-associated signaling. Importantly, in vivo studies demonstrate that CIDD-8633 effectively blocks PDAC tumor growth in preclinical mouse models. Additionally, combining CIDD-8633 with gemcitabine enhanced its efficacy synergistically. Mechanistically, CIDD-8633 treatment induces pro-apototic genes in PDAC cells. These findings position DDR2 as a promising therapeutic target and CIDD-8633 as a potential DDR2 inhibitor, offering new avenues for treatment of PDAC

overall_design: To investigate how CIDD-8633 inhibits cancer progresion, we treated Mia PaCa-2 cell line with 6uM CIDD-8633 for 48h, then followed by RNA-seq.

first: Chris TP

last: Do

first: Pitta

last: Prabhakar

first: Jack Y.

last: Prochnau

first: Deepika

last: Singh

first: Santosh

last: Timilsina

first: Panneerdoss

last: Subbarayalu

first: Daisy

last: Medina

first: Shahad

last: Abdulsahib

first: Saif

last: Nirzhor

first: Sajid

last: Khan

first: Guiming

last: Li

first: Srikanth

last: Polusani

first: Daohong

last: Zhou

first: Pei

first: Zhao

last: Lai

first: Yidong

last: Chen

first: Ratna K.

last: Vadlamudi

first: Mathew

last: Hart

first: Radhika

last: Amaradhi

first: Stanton

last: McHardy

first: Manjeet K.

last: Rao


title: Mapping genetic modifiers of epimutation rates identifies VIM2/4 as dosage-sensitive negative regulators of CG methylation maintenance [ATAC-seq]

first: Zhilin

last: Zhang

summary: Spontaneous epimutations—stochastic changes in cytosine methylation—can persist across generations in plants and are thought to contribute to phenotypic variation. Although epimutations are increasingly studied for their potential long-term effects, it remains unclear why their accumulation varies across genotypes. Here, we tracked DNA methylation across nine generations in ~400 mutation accumulation lineages derived from ~70 Arabidopsis Ler × Cvi recombinant inbred lines. Treating epimutation rates as quantitative molecular traits, we mapped a major QTL to a Cvi-derived deletion near VIM2 and VIM4, two genes involved in CG methylation (mCG) maintenance. We show that this deletion rapidly reduces genome-wide methylation to a lower steady-state and compromises mCG maintenance fidelity across generations, resulting in a ~1.5-fold increase in epimutation rates. Genotypes with elevated rates exhibited accelerated epigenetic drift and phenotypic divergence. Our findings support a punctuated-equilibrium model of mCG evolution, in which sudden disruptions to methylation homeostasis can destabilize epigenetic inheritance over longer time-scales.

overall_design: Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) was performed in the mutation accumulation mapping lines (MAML) population from two selected Ler × Cvi recombinant inbred lines (RILs), which exhibit contrasting spontaneous CG epimutation rates.

first: Wilma

last: Wanney

first: Robert

last: Schmitz

first: Frank

last: Johannes


title: Single-Molecule Barcoding Technology for Single-Cell Genomics

city: Carlsbad

first: Tom

address: 6155 Corte Del Cedro

department: R&D

institute: Universal Sequencing Technology Corp.

summary: Recent advances in barcoding technologies have introduced unprecedented scalability to single-cell genomic experiments. However, most large-scale studies are focused on the generation of reference cell atlases, which prioritize this goal over cost-efficiency and logistics. For large-scale, multi-million-cell studies to be routine in fields such as clinical diagnostics, drug/target discovery, genetic screening, and gene therapy, it is crucial to simplify the single-cell workflow and the generation of barcoding reagents. Here, we introduce AmpliDrop, a technology that streamlines single-cell barcoding by initiating the process using inexpensive single-copy barcodes, which are then amplified as part of the library preparation process, rather than relying on pre-synthesized multi-copy barcode pools. This strategy eliminates the need for barcoded beads and complex combinatorial indexing workflows. Additionally, cell compartmentalization is achieved using a conventional electronic pipette or a robotic liquid handler for automation, providing flexibility for any scale and number of samples. AmpliDrop can capture transcriptomes and chromatin accessibility and can also accommodate user-customized modalities for protein profiling, bacterial or viral DNA detection, and genetic perturbations without construct limitations. We showcase the discovery potential of AmpliDrop by investigating the influence of physical perturbation on cell diversity in human cortical organoids, revealing the selective vulnerability of glycolytic radial glia.

overall_design: Samples represent a mix of libraries provided as proof-of-concept of the AmpliDrop technology

first: Ivan

last: Garcia-Bassets

first: Yu

last: Xia


title: Mapping genetic modifiers of epimutation rates identifies VIM2/4 as dosage-sensitive negative regulators of CG methylation maintenance [WGBS]

overall_design: We generated a large mutation accumulation mapping lines (MAML) population by propagating ~70 Ler x Cvi recombinant inbred lines (RILs) through multiple generations of selfing


title: Mapping genetic modifiers of epimutation rates identifies VIM2/4 as dosage-sensitive negative regulators of CG methylation maintenance


title: Transcriptomic characterization of endogenous and transplanted myeloid cells of the brain

city: Stanford

first: Marius

middle: Marc-Daniel

last: Mader

address: 265 Campus Drive

institute: Stanford University

summary: The replacement of microglia with myeloid cells derived from transplanted bone marrow represents a promising cell therapeutic concept for different neurological disorders. Previous studies have primarily been based on freshly harvested grafts, permitting only limited control over cells prior to transplantation. Here, we demonstrate the ability of in vitro expanded hematopoietic stem and progenitor cells (cHSPCs) to engraft in the myeloid niche of the brain, and effectively replace endogenous microglia in vivo. This experiment compares the transcriptional profile of endogenous microglia, and graft-derived myeloid brain cells, which resulted from transplantation of either whole bone marrow, primary hematopoietic stem cells, or cHSPCs.

overall_design: Mice underwent systemic transplantation of GFP-labeled in vitro expanded hematopoietic stem/progenitor cells (cHSPC), whole bone marrow cells (wBM), or primary hematopoietic stem cells (pHSC) with subsequent CSF1R inhibition. Myeloid cells were isolated from the brain by fluorescence activated cell sorting using a CD45+CD11b+GFP+ gate for graft-derived myeloid cells and a conventional CD45low/intermediate CD11b+ gate for naïve microglia, which were derived from non-transplanted litter mates.

first: Yohei

last: Shibuya

last: Wernig


title: Gene expression changes induced by Elp1 deficiency during early myeloid differentiation [elp1]

summary: The replacement of microglia with myeloid cells derived from transplanted bone marrow represents a promising cell therapeutic concept for different neurological disorders. Previous studies have primarily been based on freshly harvested grafts, permitting only limited control over cells prior to transplantation. Here we demonstrate the ability of in vitro expanded hematopoietic stem and progenitor cells (cHSPCs) to engraft in the myeloid niche of the brain, and effectively replace endogenous microglia both in vivo and in vitro. Utilizing genetic editing of cHSPCs, we identify elongator acetyltransferase complex subunit 1 (Elp1; also known as Ikbkap; encoding for the protein IKAP) as an essential gene for the generation of cHSPC-derived myeloid cells (HDMCs). In accordance with its role as a subunit of the Elongator complex, loss of Elp1 in early-stage HDMCs led to upregulation of a gene module associated with the unfolded protein response.

overall_design: Culturally expanded hematopoietic stem/progenitor cells (cHSPC; Elp1 flox/flox;Ubc-CreER+/-) were pretreated with either 4-Hydroxytamoxifen or vehicle. Myeloid differentiation was initiated by coculture with primary glia cells. Cells were harvested and analyzed in the early myeloid differentiation stage at 48 hours of coculture.


title: Transcriptomic characterization of myeloid differentiation stages in the presence of glial cells [hdmc]

summary: The replacement of microglia with myeloid cells derived from transplanted bone marrow represents a promising cell therapeutic concept for different neurological disorders. Previous studies have primarily been based on freshly harvested grafts, permitting only limited control over cells prior to transplantation. Here, we demonstrate the ability of in vitro expanded hematopoietic stem and progenitor cells (cHSPCs) to engraft in the myeloid niche of the brain, and effectively replace endogenous microglia both in vivo and in vitro. This experiment compares the transcriptional profile of cHSPCs, cultured endogenous microglia, and cHSPCs-derived myeloid cells (HDMCs).

overall_design: Comparison of cultured hematopoietic stem and progenitor cells (cHSPCs), endogenous microglia from primary glia culture (cMG), and cHSPCs co-cultured with microglia depleted primary glial cells for 2 (d2.HDMC) or 14 days (d14.HDMC).


title: The effects of WNT mimetic R2M3-26 + RSPO2 on mouse liver cells

city: South San Francisco

first: Russell

last: Fletcher

address: 171 Oyster Point Blvd, Suite 400

department: Discovery Biology

institute: Surrozen, Inc.

summary: We compared the effects on liver cells of dosing a control antibody or a combination of an antibody-based WNT mimetic plus RSPO2 to activation Wnt signaling. We applied scRNA-seq to dissociated liver cells after each treatment.

overall_design: Mice were dosed IP with a control antibody or a combination of an IgG-based WNT mimetic plus RSPO2. From two mice for each treatment at 48-hours after dosing, the livers were perfused with a collagenase solution to dissociate the liver cells, and the dissociated cells were purified by FACS, and 10x Genomics 3' v2 scRNA-seq was applied to them.

first: Chenggang

last: Lu

first: Helene

last: Baribault

first: Caroline

last: Broderick

first: Wen-Chen

last: Yeh

first: Yang

last: Li


title: MeRIP of EpCAM+ epithelial cells from mouse esophagus

status: Public on Jul 17 2026

city: Fuzhou

first: Qingxiang

last: Gao

state: FuJian

address: Qiuyang Road No1.

institute: Fujian University of Traditional Chinese Medicine

summary: Esophageal squamous epithelial homeostasis depends on a tightly controlled balance between basal cell self-renewal and stepwise differentiation along the basal-suprabasal-superficial axis. Disruption of this balance leads to barrier dysfunction and contributes to diseases such as eosinophilic esophagitis (EoE), which is characterized by basal cell hyperplasia. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, is a key regulator of tissue homeostasis through control of mRNA stability and other post-transcriptional processes. However, the role of m6A, catalyzed by the METTL3/METTL14 complex, in the esophageal epithelium and contribution to disease pathogenesis remain largely unknown.

overall_design: We performed N6-methyladenosine methylated RNA immunoprecipitation sequencing (m6A-MeRIP-seq) to determine the transcripts and biological programs that are potentially regulated by the METTL3/14 complex in the adult mouse esophageal epithelium (wildtype).

first: Shuzhen

last: Xu

first: Tala

last: Fnu

first: Chao

last: Jing

first: Jianwen

last: Que


title: Multi-organ proteomic atlas of obesity regression in male mice

city: Odense M

first: Blagoy

last: Blagoev

address: Campusvej 55

department: Biochemistry and Molecular Biology

institute: University of Southern Denmark

summary: Obesity drives systemic metabolic dysfunction, yet how the body adapts and recovers at a system-wide level remains unclear. Here we generate a multi-organ proteomic atlas of diet-induced obesity and its regression in male mice. Using a standardized, semi-automated sample preparation workflow, we quantify 12,936 unique proteins across 15 organs and 4 timepoints. We find proteomic changes to be highly tissue-dependent with a small number of proteins displaying shared changes across multiple tissues. While proteomes of most tissues revert to lean levels after weight loss, white adipose tissue retains strong phagocytic and inflammatory responses, and brain, kidney, bone, thymus, and spleen display delayed obesity-induced alterations. We map the adipose tissue-specific immune regulators using ligand-target inference and show reduced expression of proteasomal subunits in brown adipose tissue, resulting in stalled ubiquitin turnover. Finally, we make all datasets open access and create an interactive webtool to facilitate further community-driven discovery.

overall_design: Male C57BL/6JBomTac cage-mate mice obtained from Taconic Biosciences were maintained at 22°C ± 3°C, with a 12-hour light/dark cycle, and provided food and water ad libitum. We housed three mice per enclosure unless separated due to aggressive behavior. After arrival, the mice underwent a 3-4-week acclimatization period on a low-fat diet (LFD) (Research Diets, D12450J) and received handling training. At 10 weeks of age, they were separated into two groups: a lean control group and an obesity regression group, using the minDiff R package49 to balance initial body weight, fat percentage, and fasting blood glucose levels. The mice in the obesity regression group were then switched to a high-fat diet (HFD) (Research Diets, D12492) for 18 weeks to induce obesity, before reverting to the LFD for 2, 6, or 12 weeks – representing short-, medium-, and long-term regression timepoints, respectively. The age-matched lean control mice were maintained on the LFD for the entire study period. The division of mice into timepoints was also performed using the minDiff R package. RNA was isolated from snap-frozen eWAT and iWAT for bulk RNA-seq.

first: Felix

last: Boel

first: Ellen

last: Gammelmark Klinggaard

first: Vyacheslav

last: Akimov

first: Daniel

last: Hansen

first: Uthpala

last: M L

first: Babukrishna

last: Maniyadath

first: Flora

middle: R

last: Fuglsang

first: Marc

last: Avellí

first: Simon

last: Rasmussen

first: Kim

last: Ravnskjær

first: Susanne

last: Mandrup


title: Gene expression profile in EpCAM+ epithelial cells from mouse esophagus

first: Qingxiang

last: Gao

overall_design: To define early transcriptional changes following Mettl3 loss, esophageal epithelial cells were isolated at day 6 after Sox2CreER-mediated deletion and subjected to bulk RNA-seq.

last: FNU