title: Aldehyde dehydrogenase 2 deficiency exacerbates alcohol-associated liver fibrosis

city: CHANGCHUN

first: Feiyu

last: Zhang

state: Jilin

address: renmin street

institute: the first hospital of jilin university

summary: This study investigates the role of Aldehyde Dehydrogenase 2 (ALDH2) in the pathogenesis of liver fibrosis. We performed gene expression profiling of liver tissues from wild-type (WT) and Aldh2 knockout mice subjected to a chronic fibrosis model.  This dataset aims to identify molecular mechanisms and transcriptomic alterations associated with ALDH2 deficiency in the context of alcohol- and CCl4-induced liver fibrosis.

overall_design: All experimental procedures utilized 8- to 10-week-old male C57BL/6 mice. WT and Aldh2-/- mice were fed an EtOH diet or pair-fed, and these mice were coadministered CCl4 for 8 weeks. The mice were euthanized 24 h after the last CCl4 injection. To induce liver fibrosis, Aldh2-/- mice and littermate WT controls were fed an ethanol diet or pair-fed control diet. Concurrently, mice were injected intraperitoneally with CCl4  dissolved in olive oil twice weekly for 8 weeks.


title: Regulation of gene expression by IL-12P40 heterodimers

status: Public on Jul 05 2026

city: Baltimore

first: Nevil

middle: J

last: Singh

state: Maryland

address: 685 W Baltimore St., HSF1 Rm 380

department: Department of Microbiology & Immunology

country: USA

institute: University of Maryland Baltimore

type: Expression profiling by high throughput sequencing

summary: The IL-12 family of cytokines are unique in that they are formed by heterodimerization of two proteins, encoded by distinct genetic loci. We previously reported that the shared subunit of IL-12 and IL-23, namely IL-12P40, can interact biochemically with other partners in vivo. The functional role of these potentially new heterodimeric immunomodulatory cytokines are not known. Here we use hydrodynamic delivery of plasmids encoding four of the top binding partners we identified (CD5L, Resistin-like Gamma, Clusterin and Pentatraxin V) into IL-20-p40 deficient mice, in order to profile the changes in splenic cell gene expression.

overall_design: The experiment involved the injection of expression constructs of the IL-12 protein family as plasmids in mice using hydrodynamic injection. Different versions of plasmids expressing IL-12P40 or variations therein were used.

first: Katrina

last: Gorga

first: Carly

last: Blair

first: Budha

last: Chatterjee

first: Michelle

last: Radov


title: Ontogenically distinct alveolar macrophages mediate cigarette smoke-induced inflammation and damage

city: Basel

first: Atul

last: Sethi

address: Grenzacherstrasse 124

country: Switzerland

institute: Hoffmann-La Roche

summary: We employed single-cell RNA sequencing (scRNA seq) using the 10x Genomics platform to investigate how varying durations of cigarette smoke (CS) exposure affect myeloid cells of different ontogenies in mice. Chronic obstructive pulmonary disease (COPD) is often associated with CS and the third leading cause of death. While airway-recruited macrophages contribute to COPD pathogenesis, the role of embryonic alveolar macrophages (Em-AM) remains unclear. Using a CS-induced COPD mouse model, we found that CS-triggered lung inflammation and emphysema-like tissue damage correlated with substantial changes in the lung myeloid compartment. Using fate-mapping, we showed that, while most CS-induced AM were recruited bone marrow monocyte-derived AM (BM-AM), Em-AM persisted and underwent similar inflammation- and emphysema-associated adaptations as BM-AM upon CS. Therefore, our data support that the CS-exposed niche, rather than ontogeny, is the main determinant of AM fate in COPD, and that CS-induced AM changes may be potential therapeutic targets to mitigate AM dysfunction in COPD.

overall_design: After exposure to room air (RA) or CS for 4, 12, or a combined 12 weeks of CS followed by 8 weeks of rest (12+8 weeks), myeloid cells and AM were isolated from the lungs of Ms4a3-tdTomato mice using fluorescence-activated cell sorting and subsequently analyzed by scRNA seq.

first: Marvin

last: Hering

first: Nina

last: Frey

first: Dilay

last: Cansever

first: Pablo

last: Hernández-Malmierca

first: Mika

last: Manser

first: Jordan

last: Poirot

first: Said

last: Aktas

first: Desiree

last: von Tell

first: Anna

last: Mechling

first: Kara

last: Lassen

first: Nikica

last: Miše-Racek

first: Thomas

last: Marichal

first: Emma

last: Doran


title: HN1-mediated Activation of Lipogenesis Through AKT-SREBP Signaling Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis

city: JEONJU

first: SOO MI

last: KIM

state: JEONBUK

address: GUNGIRO 20

department: PHYSIOLOGY

country: South Korea

institute: JEONBUK NATIONAL UNIVERSITY

summary: HN1 promotes the proliferation, migration, and invasion of HCC cells, partially through activation of the Akt-HN1-SREBP signaling pathway

overall_design: Total RNA obtained from isolated HepG2 cells subjected to HN1 shRNA treatment compared to unstrained control cells.

first: Hua

last: Jin

first: Ruoyu

last: Meng

first: Cong

middle: S

last: Li

first: Seong

middle: H

last: Kim

first: Ok

last: Chai

first: Young

last: Lee

first: Byung

last: Park

first: Ju-Seog

first: Soo

middle: M


title: New perspective to facioscapulohumeral dystrophy: the gut microbiome association with D4Z4 methylation

city: Antalya

first: Ceren

last: Hangul

address: Dumlupınar street

country: Turkey

institute: Akdeniz University

summary: The objective was investigated the compositional and functional features of the gut microbiota (GM) and their relation to D4Z4 methylation in Facioscapulohumeral muscular dystrophy (FSHD) patients.

overall_design: We entrolled 28 FSHD patients and 28 gender- and age-matched HCs. Methylation levels of DR1 and 5P regions were assessed by bisulfite sequencing. GM characterization was performed through 16S rRNA sequencing while faecal and circulating SCFAs, medium (MCFAs) and long (LCFAs) chain fatty acids were analysed with chromatography–mass spectrometry.

first: Ozlem

last: Koyuncu Ozyurt

first: Simone

last: Baldı

first: Dilek

last: Colak

first: Oznur

last: Tokta

first: Toygar

last: Pekcan

first: Sara

last: Bertorello

first: Marco

last: Pallecchi

first: Filiz

last: Koc

first: Cumali

last: Dolakay

first: Hilmi

last: Uysal

first: Kemal

last: Hakan Gulkesen

last: Ozcan

first: Gianluca

last: Bartolucci

first: Sibel

last: Berker Karauzum

first: Amedeo

last: Amedeı


title: Functional study of m6A methyltransferase METTL16 in drosophila development

city: hengyang

first: Juan

last: Gong

address: Hongxiang street

country: China

institute: university of south china

summary: N6-methyladenosine (m6A) is one of the most prevalent RNA modifications in eukaryotes. The METTL16 enzyme catalyzes the m6A modification at position 43 of U6 snRNA, which is very important for the 5'-splice site recognition by U6 during pre-mRNA splicing. Loss of METTL16 results in the death of mouse early embryos, making it difficult to study the function of METTL16 in development. Here we characterize METTL16 in the context of Drosophila melanogaster development. We showed that dMETTL16 localizes in nuclei of all endoreduplicating cells, such as cells in salivary glands, with a pattern coinciding with the replication timing. In addition, dMETTL16 is present in diploid cells of the gonad, suggesting that it plays a role in gonadal development. To further determine the function of dMETTL16, we used the CRISPR/Cas9 system to construct dMETTL16 mutations and discovered that mutants are semilethal at the larval stage while surviving adults are female sterile. More interestingly, a 50% reduction of U6 gene dosage leads to complete lethality of dMETTL16 mutants at the larval stage suggesting that loss of U6 function is one of the primary defects in the mutants. Using a novel antibody-based in vitro methylation assay, we proved that U6 is a substrate of dMETTL16. To determine whether the phenotypes depend on m6A methylase activity, we constructed point mutations of the active site of dMETTL16, and discovered that ovarian development was restored while maternal lethality ensures. These results suggest that dMETTL16 has important functions that are independent of its methyltransferase activity. Our study establishes Drosophila as a genetically tractable model for the study of dMETTL16’s function and can be explored to uncover additional dMETTL16 m6A targets.

overall_design: To identify the genes affected by dMETTL16 and its potential substrates, we performed RNA-seq.


title: Dysfunctional HDL Causes Platelet Apoptosis and Accelerated Thrombogenesis

city: Nashville

first: Matthew

last: Cottam

state: TN

address: 2213 Garland Avenue South 9465

institute: Vanderbilt University

summary: Our previous study suggests that the HDL from patients with Familial Hypercholesterolemia (FH) is enriched with peroxidation products, including malondialdehyde (MDA) and isolevuglandins (IsoLG), and is strikingly dysfunctional and enhances platelet abnormalities leading to atherosclerosis, yet the mechanisms are not clear. Although HDL are regarded as one of the most potent anti-apoptotic factors and oxidized HDL act as pro-apoptotic in macrophages and endothelial cells, little is known about their effect on platelets survival and susceptibility to apoptosis. Therefore, in our present study, we hypothesize that the maintenance of platelet integrity and protection against potentially deleterious proatherogenic stimuli may constitute a new biological function of HDL and thus may define a new mechanism contributing to their atheroprotective function in FH subjects.

overall_design:
To investigate the biological function of HDL in maintenance of platelet integrity and protection, platelets were isolated from platelet-rich plasma from patients with Familial Hypercholesterolemia and healthy control participants.
We then performed bulk RNA sequencing and comparatitive gene expression profiling analysis on 12-13 biological replicates per condition.

first: Karthik

last: Dhanabalan

first: Connor

last: Dennewitz

first: MacRae

middle: F

last: Linton

first: Amanda

middle: C

last: Doran

last: Yao

first: Wenliang

last: Song


title: Investigating the effects of IFN-gamma on attached and detached ovarian cancer cells

status: Public on Jul 04 2026

city: Dallas

first: Siyuan

last: Zhang

address: 6001 Forest Park Rd

department: Department of Pathology

institute: UT Southwestern Medical Center

summary: The interplay between intrinsic and niche-driven mechanisms that enables DTCs to survive and home to distant organs remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) coupled with velocity analyses in ascites and metastasis-bearing omenta uncovered an emergent and distinct interferon-gamma centric transcriptional trajectory, enriched among early seeding clones. Knockout of IFN-gamma receptor 1 (Ifngr1) in tumor cells significantly reduced metastatic burden and extended survival, underscoring the importance of tumor cell intrinsic IFN-gamma signaling in ovarian cancer metastasis. We identified that the tumor intrinsic IFN-gamma response and ascites-derived tumor-associated macrophages (TAMs) protect cancer cells from anoikis-mediated death. To investigate the mechanism underlying increased cancer cell survival under IFN-gamma treatment and ULA conditions, we performed bulk RNA-sequencing. We discovered increased expression of the anti-apoptotic gene Parp14 in cancer cells treated with IFN-gamma, specifically under ultra low attachment conditions.

overall_design: 3.0x10^5 Ifngr1-KO or sgNTC ID8 p53-/- cells were plated onto 6-well ULA and regular treatment plates. Recombinant IFNg (100 ng/ml) or vehicle (1xPBS) was added to corresponding wells 24 hours post initial seeding. Cells were harvested 24 hours post IFNg treatment. ULA samples were subjected to dead cell removal and total RNA was extracted using Direct-zol RNA Miniprep kit with TriReagent following the manufacturer protocol. Purified RNA was subjected to library preparation. Resulting cDNA was subjected to amplification and indexing. Final libraries were sequenced on a NovaSeq-X instrument.

first: Emilija

last: Aleksandrovic


title: miRNA sequencing of plasma sEVs from diabetic foot rats treated with tibial cortex transverse transport

city: Nanning

first: Sijie

last: Yang

state: Guangxi, P. R.

address: No.6, Taoyuan Road

department: Department of Plastic and Aesthetic Surgery

institute: The People’s Hospital of Guangxi Zhuang Autonomous Region

type: Non-coding RNA profiling by high throughput sequencing

summary: This study aimed to characterize the miRNA expression profile of plasma-derived small extracellular vesicles (sEVs) from diabetic foot rats treated with tibial cortex transverse transport. Plasma sEVs were isolated from peripheral blood samples of diabetic foot rats treated with either tibial transverse transport or sham surgery, followed by small RNA sequencing. Differentially expressed miRNAs were analyzed to explore the potential regulatory mechanisms by which tibial transverse transport promotes diabetic wound repair, with particular focus on angiogenesis, inflammatory regulation, immune modulation, and tissue regeneration.

overall_design: Peripheral blood plasma samples were collected from rats in the Sham and tibial cortex transverse transport groups. Small extracellular vesicles were isolated from plasma, and total RNA was extracted for small RNA library construction and high-throughput miRNA sequencing. Differential miRNA expression analysis was performed to identify plasma sEV-associated miRNAs altered by tibial transverse transport in diabetic foot rats.

first: Qikai

last: Hua


title: Dosage-dependent role of Gata3 in primitive endoderm and trophectoderm specification in embryonic stem cells [scRNA-Seq]

status: Public on Jul 06 2026

city: Austin

first: Jonghwan

last: Kim

state: TX

address: 2506 Speedway

institute: University of Texas at Austin

summary: Transcription factors (TFs) are critical regulators of cell fate decisions, and their intricate balance determines lineage specification during early development. Gata3 is a well-established TF in the trophectoderm (TE) development, and its ectopic expression can reprogram mouse embryonic stem (ES) cells into trophoblast stem (TS) cells. Because of Gata3’s canonical role in TE, its potential involvement in primitive endoderm (PE) differentiation has remained unexamined, representing a previously overlooked avenue of investigation. Here, we reveal that Gata3 functions as a dosage-sensitive switch governing lineage commitment in mouse ES cells. Modulating Gata3 expression revealed that high levels (Gata3-H) drive TE specification, whereas lower levels (Gata3-L) promote PE differentiation, as evidenced by distinct morphological transitions, transcriptional profiles, chromatin-binding, and functional assays. Mapping targets of Gata3 revealed differential occupancy patterns at PE- versus TE-associated enhancers correlating with dose. In vitro 3D blastoid models confirmed that Gata3 dosage alone is sufficient to drive spatial segregation, with Gata3-L and Gata3-H cells preferentially localizing to PE- and TE-like compartments, respectively. Our findings highlight Gata3’s pioneer factor-like behavior, downregulation of pluripotency networks, and latent capacity to direct lineage specification beyond its classical TE specification. These results expand the understanding of Gata family TFs in early embryogenesis and provide mechanistic insights for stem-cell based models for lineage specification.

overall_design: RNA-seq was conducted on Gata3-overexpressed mESC at low (Gata3-Low) and high (Gata3-High) levels for 0, 1, 3, 5 days of dox treatment.

first: Yeejin

last: Jang


title: RNA-seq analysis of CSNK2B and P300 knockdown in NCI-H69 small cell lung cancer cells

city: suzhou

first: Jiahao

last: Guo

address: Address: 16 Baita West Road, Gusu District, Suzhou

institute: SUZHOU MUNICIPAL HOSPITAL

summary: This submission contains bulk RNA-seq data from NCI-H69 small cell lung cancer cells transfected with negative control siRNA, CSNK2B-targeting siRNA, or P300-targeting siRNA. Total RNA was collected 48 hours after transfection. The dataset was generated to investigate transcriptional programs regulated by the CSNK2B/RBBP4/P300 complex in small cell lung cancer, particularly genes and pathways related to DNA damage repair and NF-kappa B signaling.

overall_design: Nine samples were analyzed: three biological replicates of negative control siRNA-treated NCI-H69 cells, three biological replicates of CSNK2B knockdown NCI-H69 cells, and three biological replicates of P300 knockdown NCI-H69 cells. Single-end 50 bp RNA-seq was performed on the BGISEQ platform. Differential expression comparisons were performed for si_CSNK2B versus negative control and si_P300 versus negative control.

first: Chen

last: Yuli

last: Qinnan

first: Guo

last: Jiahao

first: Li

last: Ziwei

first: Yu

last: Shaokun

first: Huang

last: Peng

first: Sun

last: Ming


title: RNASET2 degrades mRNAs that protect against lipotoxicity

city: Boston

first: Jonathan

last: Dreyfuss

state: MA

address: 1 Joslin Pl

department: Bioinformatics & Biostatistics Core

institute: Joslin Diabetes Center

summary:
Abstract/objective: RNASET2 is a lysosomal RNase whose enzymatic function is required for early events in lipotoxicity. However, the endogenous RNA substrates of RNASET2 that modulate lipid-induced cell death are not known. The purpose of this study was to identify RNASET2 substrates that impact lipotoxic stress.
Methods: RNA sequencing was used to identify RNAs that increase in abundance in human cells upon RNASET2 knockdown, and actinomycin D assays were used to show that RNASET2 impacted decay rates of these RNAs. We tested for the presence of these RNAs in immunoisolated lysosomes and determined the contribution of the lysosomal membrane transporter SIDT2 in delivery of these RNAs to the lysosome. A role for these RNAs in lipotoxic cell death was directly tested in loss- and gain of function analysis.
Results: RNASET2 knockdown increased steady-state abundance of UCHL3, PFN2 and PRDX3 mRNAs and prolonged their decay rate, leading to increased protein expression. These mRNAs were delivered to the lysosomal lumen by the lysosomal membrane transporter SIDT2 that mediates RNautophagy. While UCHL3 and PFN2 have not previously been implicated in lipotoxic responses, expression of these proteins protected against lipid-induced cell death.
Conclusions: Our study identified specific mRNA substrates of RNASET2 and uncovered a previously unexplored function for lysosomes and RNautophagy in regulation of the response to metabolic stress. Moreover, we demonstrate that RNautophagy selectively regulates turnover of specific endogenous RNAs and thereby impacts regulation of gene expression.

overall_design: RNA sequencing was performed on HEK293T cells transduced with control scramble shRNA or SIDT2 shRNA lentivirus to identify transcripts regulated by SIDT2-mediated lysosomal RNA uptake. Cells were harvested 72 h after transduction, and total RNA was extracted for library preparation and mRNA sequencing. Each condition was performed in 4 biological replicates. Differential expression analysis between control and SIDT2 knockdown samples was used to identify substrates of SIDT2-dependent lysosomal delivery.

first: Shuiling

last: Zhao

first: Stevens

last: Bontemps

first: Ryan

last: Nottingham

first: Jun

first: Mariana

last: Acuna

first: David

middle: E

last: Cohen

first: Alan

last: Lambowitz

first: Jean

last: Schaffer


title: Transcriptomic profiling of GOLM1 silenced A549 lung adenocarcinoma cells

city: Helsinki

first: Meghana

last: Nagaraj

address: Tukholmankatu 8

country: Finland

institute: Minerva Foundation Institute for Medical Research

summary: GOLM1 is a Golgi-resident protein implicated in multiple cancers, but its role in lung adenocarcinoma remains incompletely understood. RNA sequencing was performed on A549 lung adenocarcinoma cells following siRNA-mediated silencing of GOLM1 using two independent siRNAs and a non-targeting control. Differential gene expression analysis was conducted to identify molecular pathways regulated by GOLM1 depletion, including alterations in cell cycle regulation, DNA replication, lysosomal pathways, and mitochondrial-associated processes.

overall_design: RNA-seq profiling of A549 lung adenocarcinoma cells with GOLM1 knockdown(siG1 and siG2) and their respective controls (C)

first: Muhammad Yasir

last: Asghar

first: Sharath Kumar

last: Goud Emmagouni

first: Nidhina

last: Haridas

first: Vesa

last: Olkkonen


title: RNA-seq profiling of spinal cord tissues from SCI and ovariectomy-associated osteoporotic SCI mouse models

city: wenzhou

first: Quan

last: Zhou

state: zhejiang

address: Nanbaixiang street

department: Department of Spine Surgery

institute: The First Affiliated Hospital of Wenzhou Medical University

summary: Bulk RNA-seq was performed on 12 female 8-week-old C57BL/6J wild-type mouse spinal cord samples to compare transcriptomic changes among SCI7, OVX2_SCI7, and OVX8_SCI7 groups. SCI7 samples were collected 7 days after T9-T10 clip-compression spinal cord injury. OVX2_SCI7 samples were collected 7 days after SCI performed 2 weeks after ovariectomy. OVX8_SCI7 samples were collected 7 days after SCI performed 8 weeks after ovariectomy. Gene-level count, TPM, and FPKM matrices are provided as processed data.

overall_design: Twelve paired-end bulk RNA-seq libraries were analyzed: SCI7, OVX2_SCI7, and OVX8_SCI7 groups, with four biological replicates per group. The sampled tissue was the T9-T10 spinal cord injury region, including approximately 0.5 cm rostral and caudal to the lesion site. Differential expression analyses in the company report used DESeq2; downstream user analysis also compared DESeq2, edgeR, and limma-voom results.

first: Zhou

last: Quan


title: Effects of GLUT3 on transcription and translation in aged primary HUVECs

city: aaaaaaaa

first: Wanzhou

last: Wu

address: aaaaaaaaa

institute: aaaaaaa

summary: Young HUVECs were infected with lentivirus to overexpress GLUT3, and a replicative senescence cell model was established through replicative passaging. Subsequently, mRNA-seq and Ribo-seq were performed on young HUVECs, replicatively senescent HUVECs, and GLUT3-overexpressing replicatively senescent HUVECs.

overall_design: mRNA-seq and Ribo-seq of young (passage 3), aged (passage 12) and GLUT3 overexpressed aged primary HUVECs.


title: Potent type-specific de novo antibodies complement broadly reactive imprinted antibodies in immune responses to SARS-CoV-2 variants

city: Bethesda

first: Chaim

middle: A

last: Schramm

state: MD

address: 40 Convent Dr

department: Vaccine Research Center

institute: NIAID, NIH

summary: For rapidly mutating viruses such as influenza viruses and SARS-CoV-2, immune memory recalled by antigenically drifted variants primarily comprises antibodies that cross-react to the priming strain rather than de novo elicited responses, a phenomenon termed original antigenic sin or immune imprinting. The composition and functionality of de novo responses elicited by variant exposures remain unclear. Here, we isolated and characterized hundreds of recall and de novo neutralizing monoclonal antibodies after sequential exposures to SARS-CoV-2 variants in ancestral-imprinted humans. De novo variant type-specific antibodies used different V(D)J genes that were closer to germline sequence, potently neutralized future variants, and targeted distinct receptor binding domain epitopes compared to ancestral cross-reactive (recall) antibodies. Nevertheless, neutralizing responses to the updated 2024-2025 booster were predominantly ancestral cross-reactive. These results reveal the distinct contributions of imprinted and de novo antibodies to a balanced immune response and underscore the benefit of updated booster vaccines which augment both subsets.

overall_design: SARS-CoV-2 RBD specific B cells were sorted from human PBMC before and after XBB.1.5 or KP.2 mRNA-LNP vaccination. Cells were sorted into 96-well plates and sequenced using a SmartSeq-based protocol or processed using the 10x Chromium platform.

first: Timothy

last: Johnston

first: Shuk

last: Hang Li

first: Mark

last: Painter

first: Divya

last: Swaminathan

first: Reilly

last: Atkinson

first: Bernadeta

last: Dadonaite

first: Shuishu

last: Wang

first: Naomi

last: Douek

first: Lucas

last: Kampman

first: Robin

last: Carroll

first: Rachel

last: Kaxmierski

first: Bob

last: Lin

first: Leonid

last: Serebryannyy

first: Haijuan

last: Du

first: Amy

last: Henry

first: Sarah

last: Smith

first: Farida

last: Laboune

first: I-Ting

last: Teng

first: Lingshu

first: Nicole

last: Doria-Rose

first: Theodore

last: Pierson

first: Tongqing

first: Jesse

last: Bloom

first: John

last: Wherry

first: Scott

last: Hensley

first: Daniel


title: Curtailment of Toll-like receptor signalling and cytokine production in dendritic cells by secreted products of Heligmosomoides polygyrus

city: Edinburgh

first: Alasdair

last: Ivens

address: Kings Buildings

country: United Kingdom

institute: Centre for Immunity, Infection and Evolution

summary:
Dendritic cells (DCs) are the professional antigen-presenting cells responsible for recognition of pathogens and induction of appropriate adaptive immune responses. Many successful pathogens have evolved to release molecular products that can manipulate DC responses to dampen immunity. Here, we report that the excretory/secretory (ES) products of the intestinal helminth Heligmosomoides polygyrus bakeri profoundly repress the ability of murine bone marrow derived DCs to respond to canonical stimuli delivered through Toll-like Receptors (TLRs), e.g. LPS.
To further investigate the effect of HES on GMDC activation in response to LPS, we compared gene-expression profiles of LPS-treated and LPS+HES-treated cells. It was noted that HES broadly reduced the transcript levels of activation markers such as costimulatory molecules (e.g. CD40 and CD83) and pro-inflammatory cytokines (e.g. IL-12p35, LT-α and IL-23p19), and even some TLRs (e.g. TLR1 and TLR6). On the other hand, HES-treatment increased the expression of type-2 markers such as IL-33 and arginase 1, and transcripts of genes involved in cellular metabolism (e.g. HIF1A, Hmox, and Txnip).

overall_design:
C57BL/6 strain murine bone marrow-derived dendritic cells were differentiated with GM-CSF for 10 days before stimulation with either or both Heligmosomoides polygyrus Excretory-Secretory (HES) products and/or E. coli lipospolysaccharide (LPS). 3 replicate cultures were analyzed with samples taken 8 hours after stimulation.
Submitter states that IDAT files are lost.

first: Andrea

last: Kemter

first: Rick

last: Maizels


title: Investigating the contribution of early and late disseminated tumor cells in lung metastasis progression

first: Siyuan

last: Zhang

summary: Recent pioneering work in the field has not only described the presence of early neoplasm-derived cancer cells in the metastatic niche but has elucidated several underlying mechanisms responsible for their seeding. Yet, it remains unclear how early cancer cells interact with their new cellular environment once disseminated. In the present work, we aimed to address the knowledge gap related to how the immune microenvironment responds to and influences the fate of early compared to later arriving disseminated tumor cell (DTC) seeds. To distinguish early vs. late seeding cancer cells, we first engineered barcoded cancer cell lines and then conducted multiple, staggered injections in a triple negative breast cancer (TNBC) lung metastasis context. Our preliminary data showed that early timepoint injected cancer cells preferentially proliferate despite not harboring genetic and transcriptomic advantages compared to later arriving cancer cells. Furthermore, single cell RNA-seq analysis of barcoded cancer cells extracted from lung metastases and immune cells revealed an anti-inflammatory tumor associated macrophage (TAM) cluster expressing high triggering receptor expressed on macrophages 2 (Trem2) program genes and complement component q (C1q).

overall_design: We used CITE-seq (10x Genomics-based) to profile and compare transcriptomes and clonality of lung metastases. Experimental lung metastasis was initiated via E0771 mouse TNBC cancer cells injected either in a pooled fashion or sequentially into the retro-orbital sinus of wild type C57Bl/6 mice and harvested from lungs.  Lungs bearing metastases were obtained from female mice (C57Bl/6) 18 days post initial injection. There are three samples/M-HTOs that were pooled for loading onto the 10x Chromium machine. Later, three seperate libraries were prepared from each 10x lane: HTO, cell barcode (LARRY), and transcriptome. The pooled experiment contains all six BC.ID libraries and the sequential injection experiment contains: BC.ID1, BC.ID2, and BC.ID6 are used to distinguish different timepoints of injection - early, mid, and late seeding respectively. Lungs were obtained from 2-3 month old female C57Bl/6 mice with lung metastases.

first: Emilja

last: Aleksandrovic


title: snATAC-seq from K562 (ENCSR217VXJ)

status: Public on Jul 24 2026

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

institute: ENCODE DCC

type: Genome binding/occupancy profiling by high throughput sequencing

summary: For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Antigen-restricted Candida albicans Th17 cells link oral-gut immunity and adopt pathogenic features during intestinal inflammation

city: Kiel

first: Philipp

last: Hofmann

address: Michaelisstraße 5

department: Institute of Medical Immunology

country: Germany

institute: Christian-Albrecht-University of Kiel

summary: The commensal yeast Candida albicans is a major inducer of human Th17 cells. How C. albicans drives Th17 responses at homeostasis, and whether such responses contribute to inflammatory diseases, remains poorly understood. Here, we show that C. albicans-reactive Th17 cells exhibit a surprisingly narrow antigen-specificity, targeting a limited set of proteins enriched in fungal extracellular vesicles. At homeostasis, these cells predominantly reside in the oral mucosa. T cell receptor profiling reveals shared clonotypes across oral and gut tissues with C. albicans emerging as the major driver of this repertoire overlap. In Crohn’s disease (CD), C. albicans-specific Th17 cells with features of oral priming are enriched in intestinal tissues where they retain specificity for the same protein targets but acquire pathogenic Th17 traits. Together, our results reveal a stable, antigen-restricted C. albicans Th17 response shared across mucosal sites that undergoes functional adaptation in the inflamed intestine, thus representing a novel target for immune modulation in CD.

overall_design: We performed single-cell RNA and TCR sequencing of matched C. albicans-reactive T cells from peripheral blood and total CD4+ memory T cells from oral and intestinal biopsies of healthy donors (HC) and patients with Crohn’s disease (CD). The total dataset includes matched blood and intestinal biopsies from 4 HC and 10 CD patients. For a subset (4 healthy donors and 7 CD patients), matched blood, oral, and intestinal samples were obtained.

first: Gabriela

last: Rios Martini

first: Ann

middle: K

last: Kamps

first: Amos

last: Weichberger

first: Ekaterina

last: Tikhonova

first: Aidan

last: Conroy

first: Xiangyu

last: Pan

first: Diana

last: Namuch

first: Laura

last: Rathjens

first: Arne

last: Bergfeld

first: Susanna

last: Nikolaus

first: Jeanette

last: Riffert

first: Florian

last: Tran

first: Konrad

last: Aden

first: Maria

last: Witte

first: Clemens

last: Schafmayer

first: Dora

last: Stölzl

first: Stephan

last: Weidinger

first: Markus

last: Heimesaat

first: Miriam

last: Cyris

last: Härdter

first: Christof

last: Dörfer

first: Robert

last: Zarnowski

first: David

last: Andes

first: Sascha

last: Brunke

first: Bernhard

last: Hube

first: Alexander

last: Scheffold

first: Iliyan

middle: D

last: Iliev

first: Stefan

last: Schreiber

first: Petra

last: Bacher


title: Murine model of MRSA-induced kidney injury (Multiome)

city: Indianapolis

first: Takashi

last: Hato

state: IN

address: 950 W. Walnut St. R2 202

department: Medicine

institute: Indiana University

summary: Multiome RNA sequencing was performed on mouse kidneys 5 days after systemic MRSA infection. For each sample, kidneys from two individual mice were pooled.

overall_design: Female mice on a C57BL/6 background were injected intravenously with 1 x 10^7 CFU of USA300 MRSA (150 uL in PBS) based on OD-CFU calibration curves. All bacteria were cultured in tryptic soy broth. Kidney tissues were harvested 5 days post-infection. Control sample consisted of saline-treated mice that did not receive MRSA.

first: Hato

last: Takashi


title: Long non-coding RNA TTN-AS1 promotes acute liver injury in sepsis: A novel potential monitoring and therapeutic target [miRNA-Seq]

city: Chongqing

first: Jialian

last: Wang

address: Jiankang Road No.1, Yuzhong District

institute: Chongqing University Central Hospital

summary: Sepsis-associated liver injury (SALI) is a common and severe complication of sepsis that significantly affects patient outcomes. However, reliable early biomarkers and effective therapeutic targets are still lacking. In this study, we integrated whole-blood transcriptomic sequencing data and Olink inflammation-related proteomics data from SALI patients to identify key regulatory factors. By integrating weighted gene co-expression network analysis (WGCNA), differential expression profiling, and competing endogenous RNA (ceRNA) network construction, we identified the long non-coding RNA TTN-AS1 as a potential regulatory candidate. Its upregulation in SALI was further validated using a public dataset. Functional validation in a cecal ligation and puncture (CLP) mouse model demonstrated that TTN-AS1 overexpression significantly aggravated liver injury, as evidenced by elevated serum ALT and AST levels (P < 0.001), increased inflammatory cytokines IL-6 and TNF-α (P < 0.001), disrupted liver architecture and aggravated inflammatory infiltration on H&E staining, enhanced expression of apoptosis-related proteins Caspase-3 (P < 0.001) and BAX (P < 0.01), and increased hepatocyte apoptosis indicated by TUNEL assay (P < 0.001). This is the earliest report demonstrating that lncRNA TTN-AS1 contributes to the pathogenesis of SALI, highlighting its promise as a biomarker for early diagnosis and a potential target for therapy.

overall_design: To understand the transcriptional changes in the sepsis-induced liver injury group, RNA sequencing (Rna-Seq) was performed on the whole blood of 8 healthy volunteers and 8 patients with sepsis-induced liver injury.


title: Murine model of MRSA-induced kidney injury (spatial transcriptomics)

summary: Spatial transcriptomics was performed on mouse kidneys 2 datys and 4 days after systemic MRSA infection. Two consecutive slides were prepared for each time point.

sample_organism:
Staphylococcus aureus
Mus musculus

platform_organism:
Staphylococcus aureus
Mus musculus

overall_design: C57BL/6J male male, 8 weeks of age, were injected via the tail vein with USA300 JE2 MRSA. On the day of bacterial injection, S. aureus was grown to O.D. of 0.6, and the injection dose was adjusted to 5 x 10^7 CFU based on OD-CFU calibration curves. All bacteria were cultured in tryptic soy broth. Kidney tissues were harvested on days 2 and 4 post-infection. Custom probes for MRSA genes were designed according to the guidelines provided by 10X (CG000621). The following MRSA probe sets were synthesized and added to the existing mouse probe set: spa, clfA, hlgB, isdA, agrA, coa, vwb, gyrA, emp, nrdD, gluD, ackA, ccpA, ureB, arcA, rocD, nos, argH, eap, hyl, srtA, agrB, agrD, sarA, fnbA, lukG, lukH, ureA, ureC, saeR, saeS, speG, rocF, nuc, codY, sigB, fur, sigS, efp, adsA, ssl1, potD, potB


title: Long non-coding RNA TTN-AS1 promotes acute liver injury in sepsis: A novel potential monitoring and therapeutic target [RNA-Seq]


title: Examine the epigenetic consequences of KMT2D loss in melanoma using ChIP-seq profiling

city: Houston

first: Zhao

last: Zheng

address: 1901 East Rd

department: Genomic Medicine

institute: md anderson cancer center

summary: Cellular plasticity contributes to melanoma progression and resistance to treatment, but the epigenetic mechanisms driving these changes are not well understood. In a Braf-mutant mouse model, we show that loss of Kmt2d, an enzyme that adds H3K4me1 to enhancers, speeds up melanoma development and shifts cells toward a neural crest-like state. Using single-cell multiome analysis, we found that this shift is driven by increased activity of TFAP2 transcription factors, linked to changes at enhancer regions. Kmt2d loss also leads to a more immunosuppressive tumor environment, with higher levels of suppressive immune cells. This study provides the first genetic evidence that enhancer disruption plays a key role in cell identity changes in melanoma.

overall_design: ChIP-seq of histone modification H3K4me1, H3K4me3, H3k27Ac and H3k27me3 in mouse cells

first: Yingda

last: Jiang

first: Archit K.

last: Ghosh


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [scRNA-seq]

city: Summit

first: Junfei

last: Zhao

state: NJ

address: 556 Morris Ave

institute: Bristol Myers Squibb

summary: Given the well-established notion that T cells undergo significant changes in their nuclear architecture and chromatin accessibility between different stages of differentiation or phenotypic stage such as activation and exhaustion, we aimed to investigate the chromatin binding patterns of the Ikaros transcription factor, which plays a crucial role in T cell biology and gene regulation, including development, differentiation and activation in response to TCR stimulation.  However, a thorough genome-wide analysis of its occupancy and transcriptional regulatory activity between T cell activation and exhaustion has not been performed. To address this, we conducted an integrated epigenomic investigation utilizing Hi-C, ATAC-seq, RNA-seq and ChIP-seq, focusing on Ikaros and histone modifications, including H3K27ac, H3K4me1, and H3K4me3. This approach allows us to understand Ikaros-specific regulation of transcription by characterizing the epigenome in Tact versus Tex cells.

overall_design: Single-cell Multiome ATAC + Gene Expression sequencing of MM PBMCs treated with either DMSO or Mezigdomide.

first: Hsiling

last: Chiu

first: Patrick

last: Hagner


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [Hi-C]

overall_design: High-throughput Chromosome Conformation Capture (HiC) of Tact versus Tex cells (DMSO & Mezi treated).


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways

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

overall_design: Refer to individual Series


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [scATAC-seq]


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [ChIP-seq]

overall_design: ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 in Tact versus Tex cells (DMSO & Mezi treated).


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [RNA-seq]

overall_design: Transcriptome profiling (RNA-seq) of Tact and Tex cells under DMSO or Mezigdomide treatment conditions.


title: Mezigdomide reverses T cell exhaustion through degradation of Aiolos/Ikaros and reinvigoration of cytokine production pathways [ATAC-seq]

overall_design: ATAC-seq (Assay for Transposase-Accessible Chromatin with sequencing) of Tact versus Tex cells (DMSO & Mezi treated).


title: tRNA m1A modification promotes benign prostatic hyperplasia through translational regulation of the TGF-β pathway [RNA-seq]

city: Shenzhen

first: Yuhan

last: Liu

state: Guangdong

address: Xueyuan avenue 1066

institute: Shenzhen University

summary: Benign prostatic hyperplasia (BPH) is a common urological disease affecting elderly men. Although global hypermethylation has been implicated in BPH pathogenesis, the specific role of N1-methyladenosine (m1A) tRNA modifications remains unclear. Here, we find that RNA m1A modification and its methyltransferase TRMT61A were significantly upregulated in BPH tissues. Impaired m1A tRNA modification upon TRMT61A depletion resulted in decreased cell proliferation and contraction, as well as induced cell cycle arrest and apoptosis in prostate cells both in vitro and in vivo. Mechanistically, TRMT61A knockdown decreased m1A-modified tRNAs, impairing global translation and altering translational efficiency of specific genes. Moreover, ribosome profiling and RNA sequencing revealed that genes with reduced translational efficiency upon TRMT61A depletion were enriched in the TGF-β signaling pathway, including TGFβR1, INHBA, SMAD2, FST, and ID2. Codon usage bias contributed to differential translational efficiency in TRMT61A-depleted cells. Our study reveals a novel mechanism by which TRMT61A promotes BPH progression through dynamic m1A tRNA modification and modulation of a codon-dependent translational network.

overall_design: To investigate the cooperative function TRMT61A in the regulation of transcription, we established WPMY-1 cell lines in which each target gene has been knock down by shRNA

first: Libo

last: Yu

first: Xinhui

last: Liao

first: Ru

last: Huang


title: tRNA m1A modification promotes benign prostatic hyperplasia through translational regulation of the TGF-β pathway [m1A-MAP-seq]

overall_design: To investigate the cooperative function TRMT61A in the regulation tRNA m1A modification, we established WPMY-1 cell lines in which each target gene has been knock down by shRNA


title: tRNA m1A modification promotes benign prostatic hyperplasia through translational regulation of the TGF-β pathway [Ribo-seq]

overall_design: To investigate the cooperative function TRMT61A in the regulation translation, we established WPMY-1 cell lines in which each target gene has been knock down by shRNA


title: Mouse lncRNA profiling cardiac tissue

city: Muenster

first: Anika

last: Witten

address: Domagkstr. 3

department: Institute of Human Genetics, Department Genetic Epidemiology

institute: University of Muenster

type:
Expression profiling by array
Non-coding RNA profiling by array

summary:
mouse lncRNA profiling cardiac tissue
lncRNA/mRNA experssion profiling

overall_design: 9 samples, 3 groups

first: Leon

last: de Windt


title: Phenotypic CRISPR screening identifies ZBTB10 as a novel regulator of human trophoblast differentiation

status: Public on Jul 03 2026

city: Seattle

first: Meagan

middle: Nicole

last: Esbin

state: WA

address: 850 Republican St. S280

department: Obstetrics & Gynecology

institute: University of Washington School of Medicine

summary: The human placenta is built by trophoblast cells that fuse together, secrete hormones, and invade the uterus, and defects in these processes contribute to pregnancy disorders such as preeclampsia. Because cell-cell fusion and hormone secretion are inherently non-cell-autonomous processes, their regulators have remained inaccessible to conventional pooled CRISPR screens. Here, we developed an arrayed CRISPR screen in fusogenic BeWo trophoblasts that simultaneously quantifies fusion and hCG secretion across 412 gene perturbations. The screen revealed that these two hallmark functions of trophoblast differentiation are genetically separable. We characterized the strongest novel hit, ZBTB10, in trophoblast stem cells, organoids, and placental tissue and find that ZBTB10 is an essential regulator of human trophoblast differentiation. ZBTB10 is required for invasive extravillous trophoblast differentiation and supports syncytiotrophoblast maturation, establishing it as a cross-lineage regulator that both activates and represses distinct trophoblast fate programs. Together, these findings provide a genetic platform and phenotypic dissection of how regulatory networks control human placental development.

overall_design: We examined the differential expression of genes using RNASeq to determine the effects of ZBTB10 on human trophoblast differentiation using naive-pluripotent stem cell derived human trophoblast stem cells (hTSCs). We compared gene expression in wild-type versus polyclonal ZBTB10 KO hTSCs after normal hTSC culture (undifferentiated), or after 6 days of directed differentiation into extravillous trophoblasts (EVT) or syncytiotrophoblasts (STB).

middle: N

first: Min

last: Yang


title: Isoform Switching in Small Intestine Epithelial Differentiation

city: Piscataway

first: Michael

middle: P

last: Verzi

address: 145 Bevier Road

department: Genetics

institute: Rutgers, the State University of New Jersey

summary: To investigate the genome-wide isoform switching events in the small intestinal epithelium, we compared duodenal BMP 24h treated duodenal crypt organoids vs untreated duodenal crypt organoids.

overall_design: Bulk RNA-seq was employed to profile vehicle and BMP2-treated organoids.

first: Rohit

last: Aita

first: Lei

last: Chen


title: Comprehensive spatial profiling of the spleen in murine myelofibrosis identifies targetable immune-stromal interactions

city: Aachen

first: Mohamed

last: Saad

address: Pauwelsstraße 30

department: Institut für Zell- und Tumorbiologie

institute: Uniklinik RWTH Aachen

summary: Splenomegaly is a defining feature of myelofibrosis, yet the contribution of splenic mesenchymal stroma to disease progression remains unclear. We perferomed spatial transcriptomics of murine spleens to map extramedullary hematopoiesis niches. Activated red pulp reticular cells localize near hematopoietic stem and progenitor cells, and early disease shows marginal zone disruption with lymphoid depletion preceding stromal remodeling. Trajectory analyses reveal a shift of reticular cells from hematopoiesis-supportive to inflammatory and pro-fibrotic states driven by macrophage- and megakaryocyte-derived signals that activate complement and induce TNFα, TGF-β, extracellular matrix, and Thbs1 programs. Stromal deletion or pharmacological inhibition of complement component C3 suppresses these pathways, restores splenic architecture, and reduces splenomegaly and bone marrow fibrosis. These findings identify complement-dependent stromal reprogramming as a mechanism governing hematopoietic niches and a targetable axis in myelofibrosis.

overall_design: Visium Spatial Transcriptomics profiling of murine spleens from 4 conditions; WT and C3KO; ThPO-late and empty vector control

first: Bérénice

last: Dugué

first: Pia

last: Wanner

first: Mayra

last: Ruiz Tejada Segura

first: Lucas

last: Greven

first: Katrin

last: Gotz

first: Carmen

last: Schalla

first: Stijn

last: Fuchs

first: Gerjanne

last: Vroeg in de wei

first: Hélène

last: Gleitz

first: Anna Katharina

last: Galyga

first: Jessica

last: Ellen Pritchard

first: Tobias

last: Schlangen

first: Niklas

last: Lutterbach

first: Salim

last: Atakhanov

first: Lina

last: Schmidt

first: Marie

last: Parrens

first: Armelle

last: Peyrat

first: Damien

last: Luque Paz

first: Marie-Christine

last: Copin

first: Alexandre

last: Guy

first: Victor-Emmanuel

last: Brett

first: Olivier

last: Mansier

first: Susanne

last: Schmitz

first: Paul

last: Wanek

first: Bella

last: Banjanin

first: Stephani

first: Martina

last: Crysandt

first: Marian

last: Clahsen-van Groningen

first: Konnie

last: Hebeda

first: Sascha

last: Dietrich

first: Harald

last: Voehringer

first: Matthias

last: Meyer-Bender

first: Kristin

last: Séré

first: Chloé

last: James

first: Adam

last: Benabid

first: Ivan

last: Costa

first: Charles

last: Dussiau

first: Rebekka

last: Schneider


title: Phenotypic CRISPR screening identifies ZBTB10 as a novel regulator of human trophoblast differentiation [RNA-Seq BeWo]

first: Meagan

last: Esbin

overall_design: We examined the differential expression of genes using RNASeq to determine the effects of ZBTB10 on BeWo cell differentiation into syncytiotrophoblasts (STB) using Forskolin. We compared gene expression in wild-type versus polyclonal ZBTB10 KO BeWo cells in cells treated with 0.1% DMSO (undifferentiated) or treated with 20uM Forskolin for 48hrs to stimulate STB differentiation.

first: Rituja

last: Bhowmik

first: Xavier

last: Darzacq

first: Robert

last: Tjian


title: Exogenous gamma aminobutyric acid mitigates physiological and transcriptomic responses of Prunus mongolica under combined alkali salt and cadmium stress

city: Hohhot,Inner Mongolia

first: Lei

last: Wang

address: Daxue East Street, Saihan District

institute: Inner Mongolia Agricultural University

summary: Prunus mongolica is a relict xerophytic shrub with ecological importance for desert ecosystem stability and vegetation restoration in arid and semi-arid regions. However, the physiological and molecular mechanisms underlying its responses to combined alkali-salt and cadmium stress remain unclear. This study aimed to investigate the regulatory role of exogenous gamma-aminobutyric acid (GABA) in improving stress tolerance in Prunus mongolica under alkali-salt stress, cadmium stress, and their combined stress. Seedlings were subjected to eight treatments, including control, GABA alone, alkali-salt stress, cadmium stress, combined alkali-salt and cadmium stress, and the corresponding GABA-treated stress groups. Germination traits, seedling growth, physiological indices, antioxidant responses, osmotic adjustment, photosynthetic pigments, and transcriptomic profiles were analyzed to evaluate the effects of GABA at multiple biological levels. Alkali-salt, cadmium, and combined alkali-salt and cadmium stress markedly inhibited seed germination and seedling growth, with the combined stress causing the most severe damage. Stress treatments promoted reactive oxygen species accumulation, lipid peroxidation, photosynthetic inhibition, and reductions in water status and root activity. Exogenous GABA alleviated these stress-induced effects by improving germination performance, seedling growth, chlorophyll accumulation, root activity, and relative water content, while reducing oxidative damage. GABA also enhanced osmotic adjustment by increasing proline and soluble sugar contents and strengthened antioxidant defense through the activation of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, and glutathione reductase. Transcriptome analysis showed that GABA modulated stress-responsive genes associated with MAPK signaling, plant hormone signal transduction, plant-pathogen interaction, peroxisome, glutathione metabolism, photosynthesis, carbon metabolism, and other primary metabolic processes. These results suggest that exogenous GABA enhances stress tolerance in Prunus mongolica by coordinating redox homeostasis, osmotic regulation, stress signaling, photosynthetic recovery, and metabolic reprogramming under single and combined alkali-salt and cadmium stresses.

overall_design: RNA-seq analysis was performed on Prunus mongolica seedlings subjected to eight treatments: CK(control), G(GABA treatment), S(alkali-salt stress), Cd(cadmium stress), SCd(combined alkali-salt and cadmium stress), SG(alkali-salt stress with GABA treatment), CdG(cadmium stress with GABA treatment), and SCdG(combined alkali-salt and cadmium stress with GABA treatment), with three biological replicates per treatment, generating 24 libraries in total.

first: Guiquan

first: Xuebo

last: Li

first: Lu

last: Cao

first: Youwei

last: Zhang

first: Heyi

first: Xiaomin

first: Ze

last: Ren

first: Yunpeng

first: Yu


title: Phenotypic CRISPR screening identifies ZBTB10 as a novel regulator of human trophoblast differentiation [ChIP-Seq]

overall_design: We examined the binding of ZBTB10 to genomic loci using ChIP-sequencing during syncytiotrophoblast differentiation in BeWo cells. We compared genomic enrichment of ZBTB10 after immunoprecipatation using an anti-ZBTB10 antibody (Abcam, cat number ab117786, lot number 1036026-8) versus Input samples before precipitation in BeWo cells stably overexpressing N-terminally tagged Halo-3XFlag-ZBTB10 (integrated via Piggybac under an L30 promoter and Puro selection). We compared enrichment of ZBTB10 at specific genes across the genome after treatment with DMSO or Forskolin-induced differentiation relative to Input.

first: Madeleine

last: Craske


title: Effect of peripheral kappa-opioid receptor agonists on murine T cells

city: Oldenburg

first: Katharina

last: Hoffmann

address: Carl-von-Ossietzky-Straße 9-11,

institute: Carl von Ossietzky Universität

summary: This study investigated the transcriptional responses of murine T cell subsets to treatment with novel peripherally restricted, perhydroquinoxaline-derived kappa opioid receptor (KOR) agonists. We sorted and polarized primary murine CD4+ and CD8+ T cells towards Th1, Th17, Treg and CD8+ T cells and stimulated them with novel KOR agonists or vehicle control (DMSO). RNA sequencing was performed to assess gene expression changes associated with KOR activation across distinct T cell subsets.

overall_design: Bulk mRNA-sequencing  of in vitro-polarized mouse Th1, Th17, Treg and activated CD8+ T cells, treated with either vehicle DMSO or different perhydroquinoxaline-derived kappa opioid receptor (KOR) agonists in a concentration of 0.1 µM for up to five days.

first: Karin

last: Loser


title: DOT1L is essential for corneal epithelial identity and homeostasis

city: tianjin

first: Lexin

last: Yang

address: tianjin

institute: Tianjin medical university

summary: The corneal epithelium is maintained by limbal stem cells (LSCs) that differentiate into mature epithelial cells to ensure transparency and barrier function. Epigenetic regulation is critical for corneal homeostasis, yet the role of histone methyltransferase DOT1L, the sole enzyme catalyzing H3K79 methylation, remains unexplored. Here, we show that DOT1L is indispensable for corneal epithelial differentiation, postnatal development, and wound healing. Using conditional knockout mice (Dot1lflox/flox; K14-Cre), we find that DOT1L deficiency causes progressive corneal opacification, squamous metaplasia, and pathological angiogenesis. Immunofluorescence and histochemical analyses reveal that DOT1L deficiency impedes corneal epithelial differentiation, consequently inhibiting both postnatal corneal development and wound-induced corneal repair. Single-cell RNA sequencing of WT and Dot1l-KO corneas demonstrates that DOT1L loss disrupts the LSC-to-superficial-cell differentiation trajectory, and identifies Pax6, the master regulator of corneal epithelial identity, as one of the differentially expressed genes. Mechanistically, DOT1L directly deposits H3K79me2 at the Pax6 promoter to activate its transcription. Concurrently, DOT1L deficiency represses interferon signaling genes, coinciding with pathological angiogenesis. Collectively, our findings establish DOT1L as a critical guardian of corneal epithelial identity through regulation of epithelial differentiation, positioning DOT1L as a potential therapeutic target for corneal disorders.

overall_design: The eyes from 10 wild type (WT) mice and 10 Dot1l-/- mice (KO) were collected to extract corneas. The dissociated single-cell suspensions of the WT and Dot1l-KO mice corneas were subjected to 10 × Genomics sequencing.

first: Tongxin

last: He

first: Chenghao

last: Xuan

first: Yang


title: Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator

city: Stockholm

first: Danai

last: Zareifi

address: Nobels väg 6

department: Medicine Huddinge

country: Sweden

institute: Karolinska Institutet

summary: Insulin-driven gene regulation is central to adipocyte function, but the roles of many of these genes in lipid metabolism remain unclear. Here, we integrate three transcriptomic datasets to identify insulin-responsive genes and define their functions in human adipocytes using a multiparametric lipid turnover screen. Our results reveal four major clusters involved in metabolic regulation, transcription, stress responses, and lipid metabolism. Among lipid-related hits, phospholipase C X domain-containing protein-1 (PLCXD1) emerged as a regulator of insulin-stimulated lipogenesis, without affecting lipolysis or adipogenesis. PLCXD1 is induced by insulin via sterol regulatory element-binding proteins, a response attenuated in insulin resistant states. This atypical phospholipase is genetically associated with fat mass-related traits, localizes to early endosomes and catalyzes phosphatidylinositol conversion into diacylglycerol. Through structure-function analyses, we show that PLCXD1 catalytic activity is required for insulin-stimulated lipogenesis. Altogether, our results uncover PLCXD1 as an insulin-regulated enzyme linking endosomal phosphoinositide metabolism to lipid storage in adipocytes.

overall_design: RNA-seq profiling of human adipocytes generated from abdominal subcutaneous WAT of a male donor. Stromal vascular cells were isolated following collagenase digestion of the tissue. On day 12 of differentiation, cells were washed with PBS and insulin was removed from the differentiation media. On day 13, the day of the experiment, cells were washed with PBS and media was replaced with fresh differentiation media containing T3 and transferrin for 3 hours, effectively removing adipocyte-derived growth factors that induce basal insulin signaling.

first: Scott

last: Frendo-Cumbo

first: Danae

first: Mikael

last: Ryden

first: Niklas

last: Mejhert


title: Single-cell multiome profiling reveals neuronal bias of modulatory role of MeCP2 phosphorylation

city: Madison

first: Ziyao

state: WI

address: 1500 Highland Ave, Room 667

institute: University of Wisconsin-Madison

summary: MeCP2 is subject to many post-translational modifications, such as phosphorylation, in response to diverse stimuli. Several MeCP2 phosphorylation sites have been identified and studied individually. However, the combinatorial effect of phosphorylation at multiple sites has not been directly examined. Building on previous studies characterizing single mutations of MeCP2 phosphorylation sites, we created a mouse model carrying two mutations, serine 80 to alanine and serine 421 to glutamic acid (S80A;S421E, or A;E), in which the MeCP2 protein phosphorylation is fixed in a state observed in active neurons. A battery of behavioral tests was conducted to characterize the functional outcomes at the whole animal level, followed by two independent single-cell/nuclei level multiome profiling assays to characterize altered molecular pathways, and regulatory pattern biased towards glutamatergic neurons on both transcription and chromatin level. While integrated analysis of the multi-dimensional datasets identified cell-type specific molecular targets regulated by MeCP2 phosphorylation, the spatially resolved transcription profiling offered an orthogonal platform for target validation and provided additional information from spatial perspective. Together, results from this study revealed that the combinatorial effect of MeCP2 S80 and S421 phosphorylation is not merely synergistic, and the regulatory is biased towards glutamatergic excitatory neurons. More importantly, our study is the first to explore the single-cell multiomics profile changes in a MeCP2 phosphor mutant model and link it to the functional outcomes.

overall_design: snMultiome: hippocampus was separated from male mice carrying Mecp2 S80A;S421E and the WT controls at 9 week old.Joint snRNA and snATAC were prepared using the 10x Genomics platform.

first: Qiang

last: Chang


title: RNA-seq Analysis of the 5-HT2B Receptor Agonist BW723C86 on PBMC

city: shanghai

first: Yong

middle: hui

last: Chen

address: 160, Pujian Road

institute: Renji hospital

summary: This study employed RNA sequencing (RNA-seq) to investigate the effects of the 5-HT2B receptor (HTR2B) agonist BW723C86 on phagocytic function in human peripheral blood mononuclear cells (PBMCs). Primary human PBMCs were treated with BW723C86 or vehicle control（DMSO）, and transcriptomic changes related to phagocytosis were analyzed. RNA-seq data revealed significant modulation of genes involved in phagocytic pathways following HTR2B activation. Gene Set Enrichment Analysis (GSEA) demonstrated significantly upregulates phagocytosis-associated gens,including CD63,CTSA and CTSD. These findings provide molecular evidence that HTR2B activation by BW723C86 regulates phagocytic capacity in human PBMCs, suggesting a potential role for the receptor in modulating innate immune functions .

first: Yueman

first: Yonghui

first: Yue

last: Cheng


title: RNA-seq Analysis of the 5-HT2B Receptor Agonist BW723C86 on OGD-induced HT22 Cells in a Transwell Co-culture System with BMDMs

summary: Microglia and neurons engage in complex bidirectional communication that is crucial for the response to ischemic injury. To investigate the transcriptional changes underlying this crosstalk, we employed a Transwell co-culture system. Specifically, Bone marrow-derived macrophages（ BMDMs) were co-cultured with HT22 mouse hippocampal neurons subjected to 2 hours of oxygen-glucose deprivation (OGD) to model ischemic conditions. This setup allowed for the paracrine exchange of signals without direct cell contact. Following OGD, the co-culture was treated with either the 5-HT2B receptor agonist BW723C86 or a DMSO vehicle control. We then performed bulk RNA-sequencing on the microglial/BMDM population to profile their transcriptomic response to neuronal injury signals and receptor agonism. Our analysis aims to identify key signaling pathways and gene expression changes in microglia that are modulated by ischemic neurons and the serotonergic system, providing insights into the molecular mechanisms of neuroinflammation and neuroprotection.

overall_design: In this study, a Transwell co-culture system was established by seeding BV2 microglial cells (or BMDMs) in the upper chamber and HT22 hippocampal neurons subjected to 2 hours of oxygen-glucose deprivation (OGD) in the lower chamber, to model cell-cell interactions under ischemic conditions. The co-culture was treated with either the 5-HT2B receptor agonist BW723C86 or the vehicle control DMSO. Subsequently, microglial cells/BMDMs were collected from the upper Transwell inserts, and total RNA was extracted for transcriptome sequencing (RNA-seq) to analyze gene expression changes in microglia under different treatment conditions.


title: RNA-seq analysis of HaCaT keratinocytes overexpressing ATF7 under high glucose conditions

city: Luoyang

first: Pengcheng

last: Xu

address: 24 Jinghua Road

institute: The First Affiliated Hospital of Henan University of Science and Technology

summary: To investigate the downstream transcriptional targets of ATF7 in keratinocytes under high glucose conditions, we performed RNA-sequencing (RNA-seq) analysis in HaCaT human keratinocytes overexpressing ATF7.

overall_design: HaCaT cells were infected with lentivirus expressing either ATF7 (LV-ATF7) or negative control (LV-NC). After 48 hours of infection, cells were cultured under high glucose  conditions for an additional 24 h. Total RNA was extracted and subjected to high-throughput sequencing.


title: Single-cell RNA sequencing of Ms4a3-lineage myeloid cells in mouse brain after transient middle cerebral artery occlusion

city: Shanghai

address: 160 Pujian Rd

institute: Department of Anesthesiology,  Renji Hospital, School of Medicine Shanghai Jiao Tong University, China

summary: Ischemic stroke triggers a robust neuroinflammatory response characterized by the activation and infiltration of myeloid cells, including resident microglia and monocyte-derived macrophages. However, the lineage origin and temporal transcriptional dynamics of these myeloid populations remain incompletely understood.In this study, we performed single-cell RNA sequencing (scRNA-seq) on brain immune cells isolated from Ms4a3creERT2-Ai14 reporter mice, in which circulating monocyte-derived cells are permanently labeled following tamoxifen induction. Transient middle cerebral artery occlusion (tMCAO) or sham surgery was performed, and brain tissues were collected at 1 day and 3 days post-ischemia.Using single-cell analysis platform, we generated high-resolution transcriptomic profiles of brain-resident and infiltrating immune populations. Unsupervised clustering revealed distinct immune and non-immune cell types, including microglia, monocyte-derived macrophages, neutrophils, astrocytes, endothelial cells, and neurons. Comparative analysis across time points identified dynamic transcriptional changes in myeloid cell states following ischemic injury.This dataset provides a comprehensive single-cell resource to investigate the lineage tracing, heterogeneity, and temporal remodeling of brain myeloid cells in ischemic stroke.

overall_design: Ms4a3^creERT2^-Ai14 mice were administered tamoxifen (3 mg per mouse, intraperitoneally, once daily) to induce permanent tdTomato labeling of Ms4a3-lineage monocyte-derived cells. After a washout period, mice were subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery.Brain tissues were harvested at 1 day (d1) and 3 days (d3) after tMCAO, along with corresponding sham controls. Single-cell suspensions were prepared from ipsilateral brain hemispheres, and immune and non-immune cells were captured and processed using the BD Rhapsody single-cell platform according to the manufacturer’s instructions.Libraries were constructed and sequenced to generate single-cell transcriptomic profiles. Downstream analyses included quality control, dimensionality reduction, unsupervised clustering, and cell-type annotation based on established marker genes. Differential expression analyses were performed to compare cellular states across experimental conditions and time points.

first: Peiying

last: Li


title: Single-cell RNA-seq profiling of brain myeloid cells following ischemic stroke in Ms4a3-specific Htr2b conditional knockout mice

last: Zhang

summary: Brain myeloid cells, including infiltrating monocyte-derived macrophages (MDMs) and resident microglia, play essential roles in debris clearance and neuroinflammation resolution following ischemic brain injury. However, the molecular mechanisms governing the functional heterogeneity of these populations remain poorly understood. In this study, we performed single-cell RNA sequencing (scRNA-seq) to characterize the cellular and transcriptional landscape of immune and non-immune cells in the ischemic brain using a myeloid-specific Htr2b conditional knockout model. Htr2b^flox/flox mice and Htr2b^ERCre; Ms4a3-Cre mice were treated with tamoxifen to induce myeloid-lineage-specific recombination, followed by transient middle cerebral artery occlusion (tMCAO). Ipsilateral brain hemispheres were collected at 3 days post-stroke, a critical time point for inflammatory evolution and macrophage infiltration. Single-cell suspensions were generated from ischemic hemispheres, and both immune and non-immune cells were captured . This dataset enables detailed analysis of myeloid cell states, fate-mapped monocyte-derived macrophages, and the impact of Htr2b deletion on post-ischemic neuroinflammation, providing a valuable resource for studying immune regulation in ischemic stroke.

overall_design: Male and/or female adult mice were used for all experiments. Two genotypes were included: Htr2b^ERCre; Ms4a3-Cre mice and Htr2b^flox/flox littermate controls. To induce myeloid-specific recombination, mice received tamoxifen administration, followed by a 3-day washout period before ischemic surgery.  Transient focal cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO). Brains were harvested 3 days after tMCAO, and the ipsilateral hemispheres were dissected for downstream analysis. Single-cell suspensions were prepared using enzymatic digestion and mechanical dissociation.  Cells were captured without prior cell-type enrichment to preserve immune and non-immune populations and were processed for single-cell RNA sequencing using the BD Rhapsody platform according to the manufacturer’s protocol. Libraries were generated and sequenced to profile gene expression at single-cell resolution. Downstream analyses focused on identifying myeloid subpopulations, distinguishing resident microglia from infiltrating monocyte-derived macrophages, and determining the transcriptional consequences of Htr2b deletion during post-stroke neuroinflammation.


title: Integrated Single-Cell, Proteomic, and Tissue-Level Analysis Defines Cancer-Associated Fibroblast Programs in Pseudomyxoma Peritonei

city: Ghent

first: sandor

last: Dedeyne

address: C. Heymanslaan 10

country: Belgium

institute: University Ghent

summary: Pseudomyxoma peritonei (PMP) is an ultra-rare mucinous neoplasm with extensive stromal remodeling, yet the role of cancer-associated fibroblasts (CAFs) remains poorly defined. CAF are abundantly present in fibrous septae containing the mucin and regions of inflammation. We established PMP-derived CAF cultures and characterized them through multiple omics and phenotypic assays. Single-cell transcriptomic profiling revealed two distinct CAF populations: fibroblast-derived CAFs enriched for characteristic CAF functionalities and mesothelial-derived CAFs expressing mesothelial markers and pathways linked to metabolism and motility, consistent with mesothelial-to-mesenchymal transition. PMP CAFs exhibit baseline invasive and contractile properties and acquire an inflammatory CAF-like phenotype upon TNF-α/IL-1β stimulation, accompanied by altered proteomic and secretome profiles. Conditioned media from PMP CAFs further promoted macrophage polarization, highlighting their role in shaping the immune microenvironment. In conclusion, our findings reveal a previously uncharacterized role for CAF in PMP, highlighting their contribution to immune modulation in this extremely scarce peritoneal malignancy.

overall_design: A CAF culture was estbalished from a PMP tumor lesion. CAF were expanded, cryopreserved and later used for single-cell RNA sequencing to investigate teh intrinsic heterogeneity of the culture.

first: Felix

last: De Vuyst

first: Olivier

last: De Wever


title: Transcriptomic Profiling of Diabetic Porcine Wound Healing Model Identifies Key Metabolic, Inflammatory, and Oxidative Stress Pathways

city: Nashville

first: Craig

last: Duvall

address: 2414 Highland Ave

department: Biomedical Engineering

institute: Vanderbilt University

summary: Diabetic foot ulcers remain a major clinical challenge as diabetes prevalence rises, emphasizing the need for improved therapeutics and relevant preclinical models. Common rodent wound healing models poorly recapitulate human skin anatomy and repair. Although porcine skin is comparable to human skin, many studies employ young, healthy pigs that do not reflect typical diabetic human wounds. Here, we evaluated wound healing in full-thickness skin wounds in non-diabetic and diabetic Yucatan minipigs. RNA sequencing identified key transcriptional differences in wounds of diabetic versus non-diabetic animals, including pathways linked to increased inflammation and oxidative stress, as well as decreased metabolism and extracellular matrix organization, known hallmarks of diabetic wounds. These findings support this preclinical model as a powerful approach for discovery and therapeutic testing in diabetic wounds and provide a novel data set for further mining of potential gene targets for diabetic wound intervention.

overall_design: RNA-seq profililing of diabetic (STZ-induced) and non-diabetic full-thickness wounds from Yucatan minipigs at day 10

first: Joshua

middle: T

last: McCune

first: Mariah

middle: G

last: Bezold

first: Jeffrey

last: Davidson

first: C. Henrique

last: Serezani

first: Rebecca

last: Cook

middle: L


title: Truncated Gpr114-based ultrasound-hypersensitive gene circuit for controlled expression of therapeutics

city: Xi’an

first: zihang

last: li

address: 277 West Yanta Road

institute: the First Affiliated Hospital of Xi’an Jiaotong University

summary: Sonogenetics possesses significant potential for modulating cellular functions and behaviors. However, developing hypersensitive ultrasound (US)-responsive receptors presents a substantial challenge. Here, we utilized AlphaFold3 and molecular dynamics simulation technology to identify a hypersensitive Gpr114 protein variant (T-Gpr114) that can be activated by short-pulse US stimulation. We then engineered sonogentic macrophages (MΦ) using T-Gpr114 and integrated with an engineered genetic circuit, enabling high-performance expression of the nuclear factor ID3 upon short-pulse US stimulation. In mice, sonogentic-MΦ suppressed tumor growth without causing obvious toxicity and outperformed their constitutively expressing counterparts. Single-cell RNA sequencing revealed that engineered sonogentic-MΦ exhibit enhanced phagocytosis and improved recruitment of CD8+ T cells compared to cells with constitutive ID3 expression. This T-Gpr114-based US-hypersensitive gene circuit can be extended to remotely control the activation of various cell types, thereby facilitating the programming of therapeutic cells and enhancing their suitability for clinical translation.

overall_design: Fresh tumor tissues were mechanically dissociated into 1–3 mm³ pieces and enzymatically digested in a mixed enzyme solution to obtain single-cell suspensions. The resulting suspensions were filtered through 40 μm cell strainers and washed 2–3 times with buffer to remove residual debris. Cell viability was assessed using trypan blue staining and a TC20 automated cell counter (Bio-rad, Hercules, CA), and only samples with >80% viability were used for downstream processing. The cell concentration was adjusted to 700–1200 cells/μL. Subsequently, the single-cell suspensions were processed and prepared for library construction using the MobiCube® High Throughput Single Cell 3' RNA-Seq Kit (v2.1, MobiDrop) according to the manufacturer’s instructions at Novogene Bioinformatics Technology Co., Ltd (Tianjing, China).

first: Pengying

last: Wu

first: Lijun

last: Yuan


title: IVT-Free, in silico-synthesized protein-encoding RNA Oligonucleotides for rapid production of personalized cancer vaccines

city: Shanghai, China

first: Shengnan

last: She

state: Shanghai, China

address: Shanghai, China

institute: Fudan University, China

summary: Personalized mRNA neoantigen vaccines demonstrate great potential in cancer therapy, but their customization typically requires more than three months, risking the loss of the optimal therapeutic window for patients. This delay is primarily due to the reliance of current mRNA vaccine production on plasmid fermentation and in vitro transcription (IVT), which involve multiple complex steps. Chemically synthesized RNA oligonucleotides, such as antisense oligonucleotides (ASOs), are produced sparing DNA templates or IVT, thus enabling rapid manufacturing. However, ASOs are limited in length, which precludes their ability to encode proteins. Here, we introduced a 39 nucleotides cap-independent translation enhancer (CITE) element termed BBV that can drive RNA translation. Furthermore, BBV was compatible with efficient rolling circle translation (RCT). We chemically synthesized RNA oligonucleotides containing BBV and gene of interest (GOI) with characteristic 5’-OH and 3’-P termini, which could undergo circularization by endogenous RtcB RNA ligases and efficiently encode proteins through RCT in mammalian cells. We designated these RNA oligonucleotides as Protein-Encoding RNA Oligonucleotides (PEOs). Notably, compared with IVT-produced RNAs, PEOs contained undetectable levels of proinflammatory double-stranded RNAs and exhibited minimal immunogenicity. We further demonstrated that PEO-OVA (encoding OVA antigens) significantly inhibited tumor growth comparable to mRNA vaccine. In an orthotopic glioma model, PEO vaccine also exhibited therapeutic benefits with checkpoint blockade therapy. This study establishes an IVT-free RNA vaccine platform that enables rapid, safe, and highly druggable manufacturing of personalized cancer vaccines, offering substantial potential for clinical application.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq profiling of Primary T cells treated with unmodified mRNA, nucleoside-modified mRNA and nucleoside-modified circRNA. RNA-seq profiling of single cell suspension obtained by percoll of tumor from tumor-bearing mice treated with PBS or nucleoside-modified circRNA.

first: Qian

last: Pan

first: Chi

first: Xinyue

last: Wang

first: Jie

last: Yin

first: Xi

last: Chen

first: Ruitao

last: Dong

first: Ying

first: Xinyuan

last: Liao

first: Yanyan

first: Hui

last: Yan

first: Haomeng

last: Kou

first: Wanjia

first: Yong

last: Cao

last: Yang

first: Liang

last: Qu


title: Atlas of Brain-Permeable Blood Proteins Links Neuroprotection to Alzheimer's Risk Genes

city: San Francisco

first: Haoyue

last: Zhou

address: 1650 Owens St

institute: Gladstone Institutes

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

overall_design: Refer to individual Series


title: Atlas of Brain-Permeable Blood Proteins Links Neuroprotection to Alzheimer's Risk Genes [snRNAseq_microglia]

summary: The blood-brain barrier (BBB) is a highly selective interface that traditionally has been seen as restricting blood-borne substances from entering the brain. Despite its essential role in brain health and disease, the extent and functional impact of physiological blood-to-brain protein transport remain largely unexplored. Here, we use a combination of bioorthogonal chemistries, blood proteome labeling, and mass spectrometry to discover the repertoire of BBB-permeable proteins in healthy mice. We discovered that the brain vasculature actively samples hundreds of diverse circulatory proteins under physiological conditions. Many of these proteins accumulate in the brain, showing distinct enrichment patterns across both functional protein classes and anatomical brain regions. In models of neuroinflammatory and neurodegenerative diseases, the composition of BBB-permeable proteins changed significantly, implicating dysregulated protein transport in disease pathogenesis. Notably, single-injection validation experiments revealed that BBB-permeable proteins exhibit cell type-specific targeting to neurons, astrocytes, or microglia, suggesting specialized functional roles. Focusing on apolipoprotein A1 (APOA1), we demonstrate its entry via brain endothelial SCARB1 receptor, its selective accumulation in astrocytes and its interaction with the ABCA1 receptor—a critical AD risk gene that also binds APOE, the strongest genetic risk factor for late-onset Alzheimer's disease. This peripheral-central interaction promotes cholesterol efflux in astrocytes and protects neuronal synapses from degeneration. Overall, our study redefines the BBB as a dynamic conduit for the transport of specific, neuroprotective circulatory proteins into the healthy brain and establishes a molecular link between peripheral factors and Alzheimer's risk genes.

overall_design: snRNA-seq experiment examining transcriptional differences in A1AT1+ vs A1AT1- microglia in vivo

first: Jason

last: Maynard

first: Alexander

middle: J

last: Pennacchio

first: Amanda

last: Apolonio

first: Zimo

last: Zhang

first: Bella

last: Ding

first: Lei

last: Yao

first: Mina

last: Negahban

first: Janie

last: Oberhauser

first: Fionna

last: Huang

first: Yuichi

last: Chayama

first: Sahith

last: Doddipalli

first: Ning-Sum

last: To

first: Pui Shuen

last: Wong

first: Duc

last: Duong

first: Eddie

last: Fox

first: Nicholas

last: Seyfried

first: Tom

last: Cheung

first: Tara

last: Tracy

first: Al

last: Burlingame

first: Andrew


title: Regulation of cyanobacterial type IV pilus-dependent functions by interaction between a c-di-GMP receptor and two transcription factors

city: Wuhan

first: Yiling

last: Yang

state: Hubei

address: Nr.7 Donghu south road

institute: Chinese Academy of Sciences, Institute of Hydrobioloy

summary: Cyanobacteria utilize type IV pili for many behavioural responses, such as phototaxis, aggregation, floating, and DNA uptake. Type IV pilus-dependent functions are regulated by the nucleotide second messengers, c-di-GMP and cAMP. In this study, we investigated the role of a recently identified c-di-GMP receptor (CdgR) in cyanobacteria that harbours a ComFB domain. ComFB-domain proteins are widespread in cyanobacteria and are also present in heterotrophic bacteria. We demonstrated that the CdgR homolog from the cyanobacterium Synechocystis sp. PCC 6803, a model organism for studying type IV pilus-dependent functions, specifically binds to c-di-GMP. Genetic and phenotypic analyses revealed that Synechocystis CdgR is involved in phototactic motility and natural competence. Inactivation of cdgR resulted in altered expression of specific sets of minor pilins, which are essential for motility or natural competence. We identified interactions between CdgR and the CRP-family transcription factors, SyCRP1 and SyCRP2. Disruption of these CdgR-SyCRP1 and CdgR/SyCRP2 complexes is initiated by elevated c-di-GMP levels. Moreover, the assembly and stability of these complexes are influenced by other cyclic nucleotides, such as cAMP and c-di-AMP. These observed interactions imply a complex regulatory mechanism by which CdgR influences gene expression in response to cyclic nucleotide messenger signalling, particularly c-di-GMP. The present findings highlight the importance of CdgR in c-di-GMP signalling and its role in regulating type IV pilus-dependent functions in Synechocystis. The modulation of the expression of specific minor pilin genes by CdgR, through interactions with the transcription factors SyCRP1 and SyCRP2, contributes to the establishment of multiple type IV pilus functions and adaptive behaviours of cyanobacteria.

overall_design: Synechocystis sp. PCC 69803 cells (Wild-type, ∆cdgR mutant, and WT_OE cdgR overexpression) were cultured on BG11 agar plates under lateral continuous light. Cells were harvested after 5 days of growth. To collect material for RNA extraction, cells were washed from the plates using ice-cold PBS, pelleted by centrifugation, immediately frozen in liquid nitrogen, and stored at -80°C.

first: Chenliu

last: He

first: Xiaoli

last: Zeng

first: Cheng-Cai


title: Atlas of Brain-Permeable Blood Proteins Links Neuroprotection to Alzheimer's Risk Genes [snRNAseq_astrocyte]

first: Haoyue

last: Zhou

overall_design: snRNA-seq experiment examining transcriptional differences in APOA1+ vs APOA- astrocytes in vivo

first: Jason

last: Maynard

first: Alexander

last: Pennacchio

first: Amanda

last: Apolonio

first: Zimo

last: Zhang

first: Bella

last: Ding

first: Lei

last: Yao

first: Mina

first: Janie


title: Atlas of Brain-Permeable Blood Proteins Links Neuroprotection to Alzheimer's Risk Genes [bulk_RNAseq_astrocyte]

overall_design: bulk RNA-seq experiment examining transcriptional differences in APOA1+ vs APOA- astrocytes in vitro under physiological conditions

last: Negahban

last: Oberhauser

first: Fionna

last: Huang

first: Yuichi

last: Chayama

first: Sahith

last: Doddipalli

first: Ning-Sum

last: To

first: Pui Shuen

last: Wong

first: Duc

first: Eddie

first: Nicholas

first: Tom


title: Atlas of Brain-Permeable Blood Proteins Links Neuroprotection to Alzheimer's Risk Genes [bulk_RNAseq_astrocyte_AD]

first: Haoyue

overall_design: bulk RNA-seq experiment examining transcriptional differences in APOA1+ vs APOA- astrocytes in vitro when exposed to A-Beta peptide

first: Jason

last: Duong

last: Fox

last: Seyfried

last: Cheung

first: Tara

last: Tracy

first: Al

last: Burlingame

first: Andrew

last: Yang


title: Ro 08-2750 increases radiation-induced cytotoxicity in DLBCL by dysregulating DNA damage response

city: Münster

first: Lasse

last: Reichstein

state: NRW

address: Robert-Koch-Straße 31

department: Department of Radiation Oncology

institute: Münster University Hospital

summary: Introduction Current research efforts attempt to increase therapy efficacy in diffuse large B-cell lymphoma (DLBCL). Here, we evaluated the effects of small molecule inhibitor Ro 08-2750 on therapy-induced cytotoxicity in DLBCL.  Material and methods First, we established Ro 08-2750 treatment in DLBCL by verifying cell toxicity via cell viability and colony formation assays. In a next step, functional effects reducing cell viability, e.g. cell cycle dysregulation and apoptosis, were analyzed via flow cytometry. Then, we evaluated effects of Ro 08-2750 on cytotoxic therapy in cell viability and colony formation assays. After confirming an increase in irradiation-induced DNA damage via γH2AX assay, an immunoblot-based assay was used to detect changes in DNA damage response. Lastly, we analyzed Ro 08-2750-induced changes in gene and protein expression via RT-qPCR, RNA sequencing, western blot and proteomic analysis.  Results Ro 08-2750 reduces cell viability dose-dependently in DLBCL. Functionally, the decrease in cell viability is combined with a cell cycle dysregulation, specifically an increase in S phase with reduced G2/M phase, and an increase in apoptosis. DNA synthesis is reduced during S phase. Assessing the therapeutical relevance, Ro 08-2750 sensitized DLBCL cell lines to irradiation but not chemotherapy and increased irradiation-induced double strand breaks. We found a dysregulation in CHK2 phosphorylation. Moreover, Ro 08-2750 dysregulated DNA damage response in genomic and proteomic analysis.  Conclusion We identified Ro 08-2750 as a potential radiosensitizer in DLBCL. Therefore, our results indicate the potential therapeutical benefit of targeting RNA binding proteins

overall_design: RNA-seq profiling of HBL-1 cells after treatment with Ro 08-2750 or DMSO twice 24h and 5 h prior to analysis

first: Timo

last: Habig

first: Kathrin

last: Brücksken

first: Mark

last: Sicking

first: Eberhard

last: Korsching

first: Georg

last: Lenz

first: Stefan

last: Hailfinger

first: Burkhard

last: Greve

first: Fabian

last: Troschel

first: HansTheodor

last: Eich


title: Single-cell sequencing revealed the recurrence causes of ETV6::RUNX1 fusion-positive B-ALL in children

city: Jinan

first: Yunpeng

last: Dai

address: Department of Pediatric Hematology and Endocrinology 324 Jingwu Weiqi Road

institute: Shandong Provincial Hospital affiliated to Shandong First Medical University

summary: Objective: The ETV6::RUNX1 fusion is the most common genetic abnormality in childhood B-cell acute lymphoblastic leukemia (B-ALL), yet nearly 50% of relapses occur in patients initially classified as low-risk with this alteration. This study aimed to unravel the underlying pathways driving relapse in ETV6::RUNX1 positive B-ALL. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on a cohort of four B-ALL patients with the ETV6::RUNX1 fusion (three newly diagnosed and one relapsed case, selected from 25 patients). Results: we discovered that relapsed samples exhibited a decline in T cell populations, an increase in CD8 Tex cells and B cells, and a higher proportion of malignant cells.  Gene enrichment analysis demonstrated that IFN-γ response signaling pathways and inflammatory responses were significantly enriched in newly diagnosed samples.  Conversely, the relapsed samples showed enrichment in the oxidative phosphorylation and glycolysis pathways. Additionally, analysis of cellular interactions revealed that malignant B cells could interact with T cells through LGALS9-HAVCR2, potentially leading to the exhaustion of effector T cells. Moreover, NPDC1, LEF1, and ERG exhibited higher activity levels in malignant B cells from relapsed patients, highlighting their roles in the progression and maintenance of leukemia. Conclusion: In summary, our study provides valuable insights into the potential causes of relapse in B-ALL patients with ETV6::RUNX1, providing a foundation for the identification of prospective therapeutic targets.

overall_design: This study analyzed newly diagnosed and relapsed pediatric B-ALL patients at single-cell resolution, using scRNA-seq to identify relapse mechanisms in E/R cases. Our findings provide insights for developing targeted therapies to improve treatment of relapsed patients.

first: Guotao

last: Guan

first: Xiuxiu

last: Wang

first: Xiuxin

last: Li

first: Qi

first: Xiuli

first: Xiaojun

last: Sun

first: Liying

last: Liu

first: Yunfeng

last: Lu

first: Bingju

first: Xinyu

first: Ping

last: Zhao

first: Fei

last: Gao

first: Lijun

last: Chen

first: Lihua


title: Hyphae-yeast transition induced by gladiolin

city: Clayton

first: Rachael

last: Turner

state: Victoria

address: Wellington Road

department: Biochemistry and Molecular Biology

country: Australia

institute: Monash University

summary: In natural and host environments, microbes experience nutritional stress and deal with inhibitory metabolites produced by competitors within microbial populations. To adapt to such conditions, the human commensal and pathogen Candida albicans uses a cell type transition between invasive hyphae and budding yeast cells. Successful commensal colonisation and virulence of C. albicans depend upon the reversibility of this transition. Yet, while one direction - from yeast to hyphae, is well understood, the other - from hyphae back to yeast, is poorly defined. To understand it, we developed an imaging assay to visualise and quantify the hyphae-to-yeast transition in real time. Using this approach, we discovered that gladiolin, a polyketide produced by Burkholderia gladioli, accelerates the C. albicans hyphae-to-yeast transition. Mechanistically, gladiolin reprograms fungal metabolism, whereby glycolysis and ergosterol biosynthesis are up-regulated. Consequently, in the presence of gladiolin C. albicans depletes glucose more rapidly and increases ergosterol content in membranes. Building on these findings, we show that glycolysis is critical for maintaining the hyphal state. Furthermore, glucose depletion constitutes the metabolic signal for the hyphae-to-yeast transition by acting on the Ras-PKA pathway. We characterised the transcriptional programs that regulate the hyphae-to-yeast transition by balancing carbon and lipid metabolism, and propose that glycolysis provides acetyl-CoA for the biosynthesis of ergosterol to sustain membrane biogenesis during hyphal elongation. We conclude that, within fungal growth niches, changing nutritional environments and dynamic regulation of fungal metabolism control the reversible transition between hyphae and yeast and determine cell type.

overall_design: C. albicans at an OD600 of 0.1 were grown in RPMI treated with gladiolin or DMSO (control) and grown for 1 hour, 3 hours or 8 hours at 37ºC. Two independent experiments were performed.

first: Manasa

last: Bharathwaj

first: Vinzenz

last: Hofferek

first: Angavai

last: Swaminathan

first: Francios

last: Olivier

first: Maalavikha

last: Prabhakaran

first: Yu

last: Zhang

first: Malcolm

last: McConville

first: Gregory

last: Challis

first: Traude

last: Beilharz

first: Ana

last: Traven


title: Mouse kidney Methicillin-resistant Staphylococcus aureus infection time course

city: Indianapolis

first: Takashi

last: Hato

address: 950 W. Walnut St. R2 202

institute: Indiana University

summary: Bulk kidney RNA sequencing was performed on mouse kidneys after systemic MRSA infection. C57BL/6 male mice were injected via the tail vein with 5 x 10^7 CFU MRSA (USA300 JE2), and kidney tissues were harvested at days 0 (control), 1, 2, 3, 4, 7, 9, 16, and 23 post-infection.

overall_design: C57BL/6J male male, 8 – 12 weeks of age, were injected via the tail vein with USA300 JE2 MRSA. On the day of bacterial injection, S. aureus was grown to O.D. of 0.6, and the injection dose was adjusted to 5 x 10^7 CFU based on OD-CFU calibration curves. All bacteria were cultured in tryptic soy broth. Kidney tissues were harvested at the following time points: days 0 (control), 1, 2, 3, 4, 7, 9, 16, and 23 post-MRSA infection.

first: Hato

last: Takashi


title: Examine the epigenetic consequences of KMT2D loss in melanoma using ChIP-seq profiling [CUT&Run]

city: Houston

first: Zhao

last: Zheng

address: 1901 East Rd

institute: md anderson cancer center

summary: Cellular plasticity contributes to melanoma progression and resistance to treatment, but the epigenetic mechanisms driving these changes are not well understood. In a Braf-mutant mouse model, we show that loss of Kmt2d, an enzyme that adds H3K4me1 to enhancers, speeds up melanoma development and shifts cells toward a neural crest-like state. Using single-cell multiome analysis, we found that this shift is driven by increased activity of TFAP2 transcription factors, linked to changes at enhancer regions. Kmt2d loss also leads to a more immunosuppressive tumor environment, with higher levels of suppressive immune cells. This study provides the first genetic evidence that enhancer disruption plays a key role in cell identity changes in melanoma.

overall_design: To elucidate the role of KMT2D in melanoma, we used CUT&RUN sequencing to profile transcription factor and chromatin-associated protein binding involved in gene regulatory processes.

first: Zheng

first: Jiang

last: Yingda


title: Insulin modulates mPFC gene expression and emotional behavior in a sex-specific manner following fetal growth restriction

city: Verdun

first: Nicholas

last: O'Toole

state: QC

address: 6875 Boulevard Lasalle

country: Canada

institute: Douglas Mental Health University Institute

summary: Prenatal adversity, including fetal growth restriction (FR), is a major risk factor for long-term neuropsychiatric and metabolic conditions. Insulin, beyond its peripheral metabolic functions, plays a critical role in brain development and emotional regulation, particularly within the medial prefrontal cortex (mPFC). Here, we identify insulin as a mechanistic link between FR and altered behavioral responses to environmental stimuli. Transcriptomic analyses across developmental stages using the FR rodent model reveal that peripheral insulin alters gene expression in the mPFC specifically in FR animals. Pathway analyses revealed Wnt/β-catenin signaling as a common pathway across FR and insulin conditions in both sexes, but strongly in females. Moreover, targeted insulin delivery to the mPFC modifies emotional reactivity in a sex and context-dependent manner, implicating insulin signaling in shaping long-term affective outcomes in prenatally growth-restricted animals. These findings highlight a novel role for insulin in mediating the neurodevelopmental consequences of prenatal adversity.

overall_design: We used medial prefrontal cortex (mPFC) tissue samples collected from male and female Sprague-Dawley rats exposed to either fetal growth restriction (FR) or control (Ad libitum-fed) conditions. Samples were collected at three developmental stages: neonatal (P0), juvenile (P21), and adult (P90). Experimental conditions include peripheral insulin or saline administration 30 minutes before tissue collection. The dataset includes 10 biological samples for each condition and time point, allowing for comparisons across sex, age, treatment, and prenatal experience.

last: O’Toole

first: Patricia

last: Miguel


title: Thyroid cancer-associated EZH1 Q571R mutation drives chromatin compaction and H3K27me3 invasion into active chromatin

city: Seoul

first: Hanbyeol

last: Kim

address: Daehak-ro 103

institute: Seoul National University

summary: Dysregulation of Polycomb Repressive Complex 2 (PRC2) contributes to cancer. Of its catalytic subunits, Enhancer of Zeste (EZH) 1 and EZH2, EZH2 mutations are extensively studied, but the role of EZH1 in cancer remains largely unexplored. Here, we investigate the thyroid cancer-associated EZH1 Q571R mutation and uncover a mechanism that extends beyond catalytic gain of function. Using biochemical, single-molecule, epigenomic, and transcriptomic analyses, we demonstrated that EZH1 Q571R significantly enhances chromatin compaction and stimulates PRC2-EZH1 catalytic activity, thereby rewiring PRC2 chromatin interactions. This altered engagement enables PRC2 activity within H3K36me2-marked chromatin typically refractory to H3K27 methylation, leading to widespread epigenetic and transcriptional reprogramming. Notably, enhanced chromatin compaction is observed with EZH1 Q571R but not with the corresponding EZH2 Q570R mutation, indicating an EZH1-specific mechanism. Functionally, EZH1 Q571R accelerated tumor growth in vivo and induced pronounced micronuclei formation ex vivo, reflecting aberrant chromatin compaction and genome instability. Together, our study demonstrates that EZH1 Q571R promotes a permissive epigenomic landscape for the progression of follicular thyroid cancer.

overall_design: RNA-seq in Nthy cells expressing EZH1 WT, EZH1 Q571R, EZH1 Y727D, EZH1 Q571R;Y727D, EZH2 WT, or EZH2 Q570R

first: Chul-Hwan

last: Lee


overall_design: ATAC-seq in Nthy cells expressing EZH1 WT, EZH1 Q571R, EZH1 Y727D, EZH1 Q571R;Y727D, EZH2 WT, or EZH2 Q570R


title: Transcriptome sequencing of wild-type and circpTK2-silenced HCCLM3 cell lines

city: HANGZHOU

first: Xin

last: Hu

address: YUHANGTANGROAD 866

institute: Zhejiang university

summary: The role of circPTK2 in hepatocellular carcinoma has not been reported. In our study, circPTK2 expression was reduced after transfection of HCCLM3 cell lines with specific siRNA and changes in downstream signaling pathways were explored by transcriptome sequencing

overall_design: In order to study the effect of circPTK2 silencing on the downstream signaling pathway of HCCLM3 cell line, transcriptome sequencing was performed on 4 groups of wild-type and 4 groups of circPTK2-silenced HCCLM3 cells, respectively

first: Ronggao

last: Chen

first: Guanrong

first: Xiao

last: Xu