title: Developmental exposure to methyl ester sulfonate induces autism-like behavioral  deficits in mice by dysregulation of the Notch/Hes signaling pathway disrupting  neuronal differentiation

city: Nanjing

first: Liehai

last: Hu

address: 22 Hankou Road, Nanjing 210093, P. R. China

department: Medical school

institute: Nanjing University

summary:
 Developmental exposure to environmental pollutants is increasingly recognized as a
 significant risk factor for autism spectrum disorder (ASD), yet the specific mechanisms
 by which individual toxicants contribute to this neurodevelopmental disorder remain
 largely unknown. Methyl ester sulfonate (MES), a widely used anionic surfactant with
 widespread environmental detection, lacks comprehensive evaluation for
 developmental neurotoxicity. Here, we exposed pregnant mice to environmentally
 relevant MES doses (0.06–6 mg/L) from gestational day 8.5 (GD8.5) to postnatal day
 21.5 (PND21.5) and assessed their offspring for neurodevelopmental changes. Results
 showed dose-dependent ASD-like behavioral deficits, including impaired social
 interactions, heightened anxiety-like behaviors, and increased repetitive/stereotypic
 patterns. These behavioral anomalies were accompanied by neuropathological
 alterations, including blood-brain barrier (BBB) disruption, neuronal loss, and reduced
 dendritic spine density, indicative of impaired synaptogenesis. Integrative
 transcriptomic analysis of hippocampal tissue revealed significant dysregulation of key
 pathways involved in neurodevelopment, prominently featuring the Notch/Hes signaling
 pathway. Molecular docking simulations suggested that MES could directly interactwith Notch receptors, potentially disrupting ligand-receptor interactions. Further in vitro
 experimental validation demonstrated that MES exposure suppressed neural stem cell
 differentiation. Collectively, these findings provided evidence that early-life MES
 exposure acts as a neurodevelopmental toxicant by disrupting Notch/Hes signaling,
 thereby impairing neuronal differentiation and synaptogenesis, which underlied the
 observed ASD-like behavioral deficits in mice. This study offers novel mechanistic
 insights into how environmental factors contribute to ASD pathogenesis and highlights
 the need for toxicological assessment of widely distributed surfactants.

overall_design: Mice were continuously exposed to MES from embryonic stage to adulthood using a free-drinking method, and genes significantly differentially expressed in the hippocampus were detected using RNA-seq and mechanistically validated in a cellular model.

first: Ke

last: Ren

first: Yunhui

last: Xia

first: Dongmei

last: Li


title: CARD11 gain of function upregulates BCL2A1 and promotes resistance to targeted therapies combination in B-cell lymphoma [scRNA-seq]

status: Public on Dec 01 2025

city: Nantes

first: David

last: Chiron

address: 8 quai Moncousu

country: France

institute: CRCI2NA, INSERM_U1307, CNRS_6075, Nantes_Université

type: Expression profiling by high throughput sequencing

summary: Strategy combining targeted therapies is effective in B-cell lymphomas such as mantle celllymphoma (MCL), but acquired resistances remain a recurrent issue. Herein, we performed integrative longitudinal genomic and single-cell RNA-seq analyses of MCL patients treated with targeted therapies against CD20, BCL2 and BTK (i.e., OAsIs trial). We revealed the emergence of subclones with a selective advantage against OAsIs combination in vivo and showed that resistant cells were characterized by BCR-independent overexpression of NFkB1 target genes, especially due to CARD11 mutations. Functional studies demonstrated that CARD11 gain of function not only resulted in BCR independence, but also directly increase the transcription of the antiapoptotic BCL2A1, leading to venetoclax and OAsIs combination resistance. Based on the transcriptional profile of OAsIs-resistant subclones, we designed a 16-gene resistance signature that was also predictive for MCL patients treated with conventional chemotherapy, underlying a common escape mechanism.

overall_design: 7 bone marrow samples from 6 patients included in the OAsIs trial were analyzed in single cell RNA sequencing (scRNA-seq). Briefly, live MCL cells were first enriched by Ficoll-Paque Plus and anti-human CD19 magnetic beads. Depletion of human erythroid precursors and erythrocytes was then performed using CD235a (Glycophorin-A) magnetic beads. 15,000 cells from the resulting suspensions were loaded on a Chromium controller to generate single-cell partitions following the manufacturer’s protocol (10X genomics). scRNA-seq libraries were constructed using the Chromium Next GEM Single Cell 3’ GEM, Library & Gel Bead Kit v3.1 and sequenced using the NovaSeq 6000 system (Illumina).

first: Salomé

last: Decombis

first: Céline

last: Bellanger

first: Yannick

last: Le Bris

first: Candice

last: Madiot

first: Jane

last: Jardine

first: Juliana

last: Carvalho Santos

first: Delphine

last: Boulet

first: Christelle

last: Dousset

first: Audrey

last: Menard

first: Charlotte

last: Kervoelen

first: Élise

last: Douillard

first: Philippe

last: Moreau

first: Stéphane

last: Minvielle

first: Agnès

last: Moreau-Aubry

first: Benoit

last: Tessoulin

first: Gael

last: Roué

first: Nicolas

last: Bidère

first: Steven

last: Le Gouill

first: Catherine

last: Pellat-Deceunynck


title: Cell cycle arrest enhances CD8+ T cell effector function by potentiating glucose metabolism and IL-2 signaling

city: Leiden

first: Ramon

last: Arens

address: Albinusdreef 2

department: Immunology

country: Netherlands

institute: Leiden University Medical Center

summary: Cell cycle-inhibiting chemotherapeutics are widely used in cancer treatment. Although their primary aim is to block tumor cell proliferation, their clinical efficacy also involves specific effector CD8+ T cells that undergo synchronized proliferation and differentiation. How CD8+ T cells are programmed when these processes are uncoupled as occurs during cell cycle inhibition is unclear. Here, we demonstrate that activated CD8+ T cells arrested in their cell cycle can still undergo effector differentiation. Cell-cycle arrested CD8+ T cells become metabolically reprogrammed into a highly energized state, enabling rapid and enhanced proliferation upon release from arrest. This metabolic imprinting is driven by increased nutrient uptake, storage, and processing, leading to enhanced glycolysis in cell cycle-arrested cells. The nutrient sensible mTORC1 pathway, however, was not crucial. Instead, elevated IL-2 production during arrest activates STAT5 signaling, which supports expansion of the energized CD8+ T cells following arrest. Transient arrest in vivo enables superior CD8+ T cell-mediated tumor control across models of immune checkpoint blockade, adoptive cell transfer, and therapeutic vaccination. Thus, transient uncoupling of CD8+ T cell differentiation from cell cycle progression programs a favorable metabolic state that supports the efficacy of effector T cell-mediated immunotherapies.

overall_design: To investigate the mechanisms underlying enhanced cell cycle progression after temporal cell cycle arrest, we characterized the transcriptional activity in unstimulated, arrested, released and non-arrested CD8+ T cells. To this end, we made single cell suspensions from pooled spleen samples from mice. CD8 T cells were enriched and we had 4 different conditions: unstimulated (60 hours), blocked (60 hours stimulated with aCD3 and aCD28 in the presence of hydroxyurea), non-arrested (60 hours stimulated with aCD3 and aCD28) or released (stimulated with aCD3 and aCD28 in the presence of hydroxyurea which was washed away. These cells could proliferate for 60 hours. Next, live CD8 T cells were sorted (BD FACS aria). For the "non-arrested" and "released" conditions only the cells that had at least 1 cell division were selected on the basis of CFSE dilution. Next, gene expression profiling analysis was performed using data obtained from RNA-seq of the four different conditions.

first: Floortje

middle: J

last: van Haften

first: Tetje

middle: C

last: van der Sluis

first: Hanna

middle: S

last: Hepp

first: Nils

last: Mülling

first: Reza

last: Nadafi

first: Bharath

last: Sampadi

first: Suzanne

last: van Duikeren

first: Shirin

last: Mostert

first: Rosemarijn

last: van der Sterre

first: Peter

middle: A

last: van Veelen

first: Graham

last: Heieis

first: Dominique

middle: M

last: Veerkamp

first: Thomas

middle: H

last: Wesselink

first: Ward

last: Vleeshouwers

first: Macha

last: Beijnes

first: Iris

middle: N

last: Pardieck

first: Eralin

middle: L

last: van Horssen

first: Anne

middle: F

last: de Groot

first: Manon

last: van der Ploeg

first: Judith

middle: R

last: Kroep

first: Noel

last: de Miranda

first: Sabina

middle: Y

last: van der Zanden

first: Jacques

last: Neefjes

first: Hailiang

last: Mei

first: Alfred

last: Vertegaal

first: Bart

last: Everts

first: Sjoerd

last: van der Burg


title: Transcriptome analysis during sex reversal in Monopterus albus

status: Public on Nov 30 2025

city: Wuhan

first: Yuan

last: Zhao

address: Donghu Road 7th

country: China

institute: Institute of Hydrobiology, Chinese Academy of Sciences

summary: The rice field eel (Monopterus albus) is an economically important freshwater-farmed fish with natural sex reversal characteristics, which results in low egg production and seedling shortage. Limited epigenomic and transcriptomic information during sex reversal hinders research on the reproductive development of Monopterus albus. In this investigation, 9 key stages during sex reversal were collected for multi-omics experiments, including PacBio Iso-seq, RNA-seq and ATAC-seq. Through combined analysis of Iso-seq and RNA-seq, we constructed more accurate transcript annotation than those from NCBI. A total of 37,911 unannotated transcripts were obtained, including transcripts from novel genes and alternative splicing structures, etc. The noteworthy point is that our annotations have more precise polyA locations. In addition, we identified multiple potential cis-regulatory elements with high confidence based on changes in chromatin accessibility by ATAC-seq, providing precise targets for regulating gene expression and thereby modulating gonadal development. In summary, we provides a comprehensive and convenient data resource for studying sex reversal-related mechanisms from multiple perspectives.

overall_design: RNA-seq profiling of  female (PVO, VO, and MO stages), intersex (ISE, ISM,  and ISL stage), and male ( ES, MS, and LS stage) during sex reversal in Mpnopterus albus.


title: Omega-3 reverses the metabolic and epigenetically regulated placental phenotype acquired from preconceptional and peri-conceptional exposure to air pollutants

city: los angeles

first: Shubhamoy

last: Ghosh

state: CA

address: 650 Charles E Young  Dr East

department: Pediatrics

country: USA

institute: University of California Los Angeles

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: CARD11 gain of function upregulates BCL2A1 and promotes resistance to targeted therapies combination in B-cell lymphoma

first: David

last: Chiron

summary: Strategy combining targeted therapies is effective in B-cell lymphomas such as mantle cell lymphoma (MCL), but acquired resistances remain a recurrent issue. Herein, we performed integrative longitudinal genomic and single-cell RNA-seq analyses of MCL patients treated with targeted therapies against CD20, BCL2 and BTK (i.e., OAsIs trial). We revealed the emergence of subclones with a selective advantage against OAsIs combination in vivo and showed that resistant cells were characterized by BCR-independent overexpression of NFkB1 target genes, especially due to CARD11 mutations. Functional studies demonstrated that CARD11 gain of function not only resulted in BCR independence, but also directly increase the transcription of the antiapoptotic BCL2A1, leading to venetoclax and OAsIs combination resistance. Based on the transcriptional profile of OAsIs-resistant subclones, we designed a 16-gene resistance signature that was also predictive for MCL patients treated with conventional chemotherapy, underlying a common escape mechanism. Among druggable strategies to inhibit CARD11-dependent NFkB1 transduction, we evaluated the selective inhibition of its essential partner MALT1. We demonstrated that MALT1 protease inhibition led to the reduction of genes involved in OAsIs resistance, including BCL2A1. Consequently, MALT1 inhibition induced synergistic cell death in combination with BCL2 inhibition, irrespective of CARD11 mutational status, both in vitro and in vivo. Taken together our study identified mechanisms of resistance to targeted therapies and provided a novel strategy to overcome resistance in aggressive B-cell lymphoma.

overall_design: RNA-seq expression in BCL2A1 + CARD11 WT cell lines (SP53, NTS3, REC-1) and BCL2A1+ CARD11 MUT cells (001-124, OCILY3, SUDHL16) treated 24h with the BTK inhibitor Ibrutinib (500 nM) or the MALT1 inhibitor MLT-748 (1 μM)

first: Salomé

last: Decombis

first: Céline

last: Bellanger

first: Yannick

last: Le Bris

first: Candice

last: Madiot

first: Jane

last: Jardine

first: Juliana

last: Carvalho Santos

first: Delphine

last: Boulet

first: Christelle

last: Dousset

first: Audrey

last: Menard

first: Charlotte

last: Kervoelen

first: Élise

last: Douillard

first: Philippe

last: Moreau

first: Stéphane

last: Minvielle

first: Agnès

last: Moreau-Aubry

first: Benoit

last: Tessoulin

first: Gael

last: Roué

first: Nicolas

last: Bidère

first: Steven

last: Le Gouill

first: Catherine

last: Pellat-Deceunynck


title: ISO-seq analysis during sex reversal in Monopterus albus

first: Yuan

last: Zhao

overall_design: ISO-seq of mixture of female (PVO, VO, and MO stages), intersex ((ISE, ISM,  and ISL stage), and male ( ES, MS, and LS stage) during sex reversal in Mpnopterus albus.


title: SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells

city: Iowa City

first: Pak Hin Hinson

last: Cheung

state: Iowa

address: 51 Newton Raod

department: Department of Microbiology and Immunology

institute: University of Iowa

summary: Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) restricts a broad spectrum of viruses through multifaceted mechanisms. It also limits spontaneous- and virus-induced innate immune responses by suppressing proinflammatory cytokine and type-I interferon (IFN-I) production. Some viruses escape SAMHD1 restriction and utilize SAMHD1-mediated innate immune suppression to establish effective infection through IFN antagonism. Our previous studies showed that SAMHD1 is a proviral factor facilitating replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in human macrophages, monocytic THP-1 and epithelial-like HEK293T cell lines by suppressing IFN responses. However, it is unclear about the function of SAMHD1 in lung epithelial cells during SARS-CoV-2 infection. Here, we report that SAMHD1 knockout (KO) restricts SARS-CoV-2 replication in lung epithelial Calu-3 cells by suppressing endogenous expression of the viral receptor angiotensin-converting enzyme 2 (ACE2) via hepatocyte nuclear factor 1-alpha (HNF1α) and HNF1β. Using pseudotyped SARS-CoV-2 and lentiviral vectors, we found that SARS-CoV-2 spike protein-mediated viral entry was suppressed in SAMHD1 KO Calu-3 cells. SAMHD1 KO repressed ACE2 expression in Calu-3 cells at mRNA and protein levels. Functional analyses revealed that HNF1α and HNF1β were crucial for the endogenous ACE2 expression in Calu-3 cells. Additionally, SAMHD1 KO led to a reduction in the expression levels and ACE2-promoting function of HNF1α and HNF1β. Inhibition of IFN antiviral response by baricitinib, a Janus kinase 1 and 2 (JAK 1/2) inhibitor, did not revert the suppression of SARS-CoV-2 in SAMHD1 KO Calu-3 cells. SAMHD1 knock-in and deoxynucleoside supplementation experiments indicated that SAMHD1 expression and dNTP pool balance collectively regulated HNF1-mediated ACE2 expression in Calu-3 cells. Our findings demonstrate that SAMHD1 depletion hinders HNF1-mediated ACE2 expression and SARS-CoV-2 replication in Calu-3 cells via a novel mechanism beyond its IFN-suppressive function.

overall_design: To gain mechanistic insight, mRNA-seq was performed to profile the transcriptome of SAMHD1 knockout Calu3 cells (KO) and compared with that of the control Calu-3 cells (Ctrl). Two clones of KO cells were generated through CRISPR/Cas9 with one single guide RNA having different target sequences. Ctrl cells were mock control treated similarly as the KO cells but were transduced with empty vector. 8 x 105 Calu-3 Ctrl, KO1 and KO2 cells were seeded in 6 well plates in biological triplicate. Cells were cultured in 2mL DMEM/F12 with 20% FBS, 100 U/mL penicillin, and 100 µg/mL streptomycin. At 20 hours after seeding, cells were washed once with DPBS and lysed with RLT plus lysis buffer. Cellular RNA was purified with RNeasy Plus kit following manufacturer’s instructions. All RNA samples got RNA integrity Number (RIN) scores equal to or more than 9.9 as determined by Agilent BioAnalyzer by Genomics Division of Iowa Institute of Human Genetics (University of Iowa). RNA samples were processed through Illumina Stranded mRNA Prep (illumina) and sequenced by Element Aviti24 using Cloudbreak FS-High output flow cell at 150 cycle (2x75) by the Genomics Division.

first: Pearl

last: Chan

first: Hua

last: Yang

first: Krisztina

last: Ambrus

first: Shravya

last: Honne

first: Baek

last: Kim

first: Stanley

last: Perlman

first: Li

last: Wu


first: Shubhamoy

last: Ghosh

summary: We report the distribution of 5-Hydroxymethylation mark by Next Generation Sequencing from Gestational D19 mouse exposed to Air -Pollutant material with or without prior treatment with Fish Oil.

overall_design: Examination of DNA methylation pattern in mouse placenta during gestational exposer to Air pollutant material and impact of fish oil treatment.

first: Amit

last: Ganguly

first: Bo-Chul

last: Shin

first: Peng

last: Jin

first: Sherin

last: Devaskar


summary: We report the distribution of methylation mark by Next Generation Sequencing (RRBS) from Gestational D19 mouse exposed to Air -Pollutant material with or without prior treatment with Fish Oil.


title: Chromatin accessibility analysis during sex reversal in Monopterus albus

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: ATAC-seq profiling of  female (PVO, VO, and MO stages), intersex ((ISE, ISM,  and ISL stage), and male ( ES, MS, and LS stage) during sex reversal in Mpnopterus albus.


title: Pluripotency factor OCT4 enhances the firing efficiency of late DNA replication origins in mouse em-bryonic stem cells [EdUseq]

city: Geneva

first: Vasilis

last: Dionellis

address: 30, quai Ernest-Ansermet

country: Switzerland

institute: University of Geneva

summary: DNA replication initiates at specific genomic regions known as initiation zones (IZs), which follow a defined spatiotemporal program partially dependent on cell type. Here, we examined the replication initiation patterns of pluripotent mouse embryonic stem cells (mESCs), which are characterized by a very short G1 phase and rapid entry into S phase. Using EdU-seq combined with cell cycle synchroni-zation and Repli-seq, we identified IZs, that are activated during S phase in mESCs and classified them as early, mid, or late, according to the replication timing (RT) domain to which they mapped. Remarka-bly, we found that some IZs mapping to mid or late RT domains were activated within 1–2 hours of entry into S phase. Chromatin and nascent transcriptome profiling revealed that these IZs were associated with regions of open chromatin structure that were bound by the pluripotency factor OCT4. Transient OCT4 depletion was associated with reduced chromatin accessibility and replication initiation efficiency at these sites. These results provide an example of a pioneer factor, OCT4, facilitating DNA replication initiation by promoting local chromatin accessibility.

overall_design: Monitor DNA replication by EdUseq

first: Eddie

last: Rodriguez-Carballo

first: Sotirios

middle: G

last: Ntallis

first: Lilia

last: Bernasconi

first: Ezgi

last: Keskin

first: Thanos

middle: D

last: Halazonetis


title: A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure [ncRNA-Seq]

city: Chicago

first: Ivan

last: Moskowitz

state: IL

address: 900 East 57th Street, KCBD Room 5102

institute: Univeristy of Chicago

type: Non-coding RNA profiling by high throughput sequencing

summary: Atrial fibrillation (AF) and heart failure (HF) frequently co-occur and exacerbate each other's morbidity, yet the underlying molecular mechanisms remain incompletely understood. Here, we compared atrial gene regulatory networks across multiple mouse models of AF (Tbx5 cKO, Zfhx3 KO, Scn1b-null) and HF (TAC, AngII), revealing unexpected transcriptional and genomic convergence between Tbx5 cKO and HF models. Notably, Tbx5 was significantly downregulated in atrial tissue from both murine and human HF samples. We identified over 100 coordinately dysregulated Tbx5- and TAC-dependent transcription factor genes, with cell-type resolution achieved through single-cell transcriptomics. Loss of a TBX5-driven cardiomyocyte gene regulatory network—including Klf15, a transcriptional repressor of hypertrophy—was observed in both AF and HF models, while a shared disease-specific network emerged in activated fibroblasts, notably involving the pro-fibrotic regulator Sox9. These findings define a conserved TBX5-dependent atrial genomic injury response that may underlie the reciprocal pathophysiological relationship between AF and HF.

overall_design: non-coding RNA-seq profiling of left atrial tissue from sham vs. TAC, Day 9 post-surgery

first: Sonja

last: Lazarevic

first: Carlos

last: Perez-Cervantes

middle: P

first: David

last: Park

first: Junhua

last: Xiao


title: Epigenetic modification, as a distinctive therapeutic molecule for Parkinson’s disease gene therapy.

city: Seoul

first: Yujung

last: Chang

address: 98 Hannamdaero, Yongsan-gu

country: South Korea

institute: Stand Up Therapeutics Inc.

summary: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons (DN) in the substantia nigra and disruption of cellular maintenance. Here, we demonstrate that NDST3-mediated epigenetic reprogramming halts neuronal degeneration and restores motor function in an animal model of PD.

overall_design: RNA-seq, CUT&RUN, ATAC-seq and scRNA-seq experiment conducted on 6-OHDA-induced PD model with NDST3 treatment.

first: Junsang

last: Yoo


title: Galectin-9 regulates CD4+ T cell proliferation via intracellular HLA-DR binding in dendritic cells

city: Nijmegen

first: Guido

last: van Mierlo

address: Geert Grooteplein Zuid 28

institute: Radboudumc

summary: To initiate T cell-mediated immunity, dendritic cells (DCs) present antigen to specific T cells through the establishment of an immune synapse. Despite its critical importance, the spatiotemporal dynamics of membrane receptor organization during synapse formation in DCs have been only partly characterized. Galectins, a family of β-galactoside binding proteins, exert crucial roles in homeostasis and pathological processes but the molecular mechanisms underlying galectin function are largely unresolved. Here, we demonstrate that intracellular galectin-9 (gal9) is required for T cell activation. Murine and human DCs lacking gal9 showed impaired induction of CD4+, but not CD8+, T cell proliferation, suggesting a conserved function for gal9 in modulating DC–T cell interactions. Live-cell imaging further revealed that galectin-9-depleted DCs fail to establish stable immunological synapses with T cells, resulting in reduced T cell clustering and activation. Unbiased co-immunoprecipitation and mass spectrometry identified HLA-II as a gal9 binding partner in DCs, and we observed a marked reduction of HLA-II recruitment to the immune synapse as the underlying mechanism. Conditional gal9 knockout in DCs led to enhanced tumor growth, compared to their WT counterparts, underscoring galectin-9 role in T cell-dependent anti-tumor immunity. Collectively, this study provides the first detailed account of gal9-mediated HLA-II organization at the synaptic site of DCs, revealing a novel mechanism by which galectins orchestrate immune receptor positioning from within the cytoplasm to enhance CD4+ T cell activation.

overall_design: Wildtype and galectin-9 knockdown dendritic cells

first: Andrea

last: Furones

first: Laia

middle: Q

last: Cano


title: A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure [HI-C]

overall_design: Adult mouse ventricular fibroblasts (AMVFs) were isolated from male C57BL/6J mice using Langendorff perfusion and enzymatic digestion with collagenase type 2. Following isolation, fibroblasts were separated from cardiomyocytes by differential sedimentation and centrifugation, then cultured and passaged once before serum starvation for 18 hours. Cells were subsequently treated with either TGF-β1 (10 ng/mL) or vehicle control for 48 hours to model fibroblast activation. Genome-wide chromatin conformation was assessed using the Arima Genomics Hi-C+ protocol. Libraries were sequenced to approximately 1 billion paired-end reads per group and processed through HiC-Pro for alignment to the mm10 reference genome.

first: Thomas

last: Vondriska

first: Timothy

last: Mckinsey


title: A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure [RNA-Seq]

summary: Transcriptomic profiles of cardiac tissue from CD1 mice subjected to sham or transverse aortic constriction (TAC) surgery, a pressure-overload mouse model. Left atrial tissue was collected 9 days post-surgery, and RNA-seq was performed to identify differentially expressed genes between sham and TAC.

overall_design: RNA-seq profiling of left atrial tissue from sham vs. TAC, Day 9 post-surgery


title: DNA methylation analysis of colonic epithelial cells from 5-AZA and DSS treated mice

city: London

first: Samuel

last: Asfaha

address: 1151 Richmond St

country: Canada

institute: Univeristy of Western Ontario

summary: Transposable elements (TEs) comprising nearly 50% of the genome are generally silenced by epigenetic mechanisms. Epigenetic anti-cancer drugs can lead to their re-expression, however, the role of TEs in tumorigenesis is unknown. Here, we demonstrate that TEs and their activation of a viral mimicry response plays an important tumor suppressive role in inflammation. We discovered that both patients and mice with colitis express TEs that lead to a viral mimicry response. Interestingly, this response inhibits stemness of cancer-initiating cells. Further activation of viral mimicry by DNA hypomethylation inhibits tumorigenesis. Conversely, knockout of the anti-viral signaling protein MAVS promotes tumorigenesis and reverses the anti-tumor effect of DNA hypomethylation, confirming a tumor suppressive role of viral mimicry. Consistent with this finding, patients with colitis-associated dysplasia show decreased expression of TEs and interferon-related genes. These findings suggest that activation of viral mimicry inhibits stemness and plays a key tumor suppressive role in inflammation.

overall_design: DNA methylation status was meaused of colonic epithelial cells isolated C57Bl6/J mice (n=3 in each group) treated with 5-AZA-2'-deoxycytidine and 2.5% dextran sodium sulfate. The mice received one dose of 5mg/kg 5-AZA-2'-deoxycytidine (5-AZA) or vehicle (saline) 2 days prior to DSS treatment for 5 days and the remaining two doses of 5-AZA, 5 and 10 days following the end of DSS treatment. 14 days post the end of DS, colonic epithelial cells were isolated from the colons of mice and bisulfite converted DNA were then hybridized to the Illumina Mouse Methylation BeadChip array.


title: SOS components differentially regulate seed germination and seedling growth under saline condition in Arabidopsis

first: DAMI

last: YANG

address: Cheonpa-ro 47 gil 100, Yongsan-gu

department: Department of Biological Sciences

institute: Sookmyung Women's University

summary: Seed germination is an important process that begins new life in plant. To ensure that seedlings grow under optimal condition after germination, seed germination should be precisely regulated by endogenous and environmental factors. Salinity is the major abiotic stress that often adversely impacts plants by inhibiting seed germination, growth and development. Comparative transcriptome analyses of salt-treated seedlings and seeds revealed that although some of the well-known salt-stress marker genes, including RD29a and DREB2A were not induced under salt, genes that can be categorized in similar GO terms involving with stress responsiveness are changed both in seeds and seedlings in response to salt treatment.

overall_design: Examination of mRNA expression patterns was conducted in imbibed seeds of Arabidopsis Col-0 and the serk1-1 mutant. Col-0 and serk1-1 seeds were incubated in liquid MS medium and MS medium supplemented with 200 mM NaCl for 24 hours.

first: Dami

last: Yang

first: Yunmi

last: Ha

first: Myeong Min

last: Lee

first: Kyoung Hee

last: Nam


title: Perinatal dysfunction of innate immunity in cystic fibrosis

city: Munich

first: Gianluca

last: Santamaria

state: Germany

address: Ismaninger Strasse 22

department: Department of Medicine I

country: Germany

institute: Klinikum rechts der Isar – Technical University Munich

summary: The study aimed to compare the gene expression profiles at a single cell level in peripheral blood (human&pig), lung-derived (pig), bone marrow (pig) mononuclear cells (MNC)  between subjects with cystic fibrosis (CF) and disease controls (WT).

sample_organism:
Homo sapiens
Sus scrofa

platform_organism:
Homo sapiens
Sus scrofa

overall_design: Cryopreserved MNC of four donors were pooled and then processed for generating single-cell RNA sequencing libriaries for each genotype, cell source and species.

first: Daniel

last: Reichart

first: Florian

last: Jaudas

first: Nikolai

last: Klymiuk


title: OsMAINTENANCE OF MERISTEM LIKE 1 controls style number at high temperatures in rice

city: MILANO

first: Vittoria

middle: Francesca

last: Brambilla

state: MI

address: via Celoria 2

department: Department of Agricultural and Environmental Sciences

country: Italy

institute: Università degli Studi di Milano

summary: OsMAIL1 encodes for a rice protein of the Plant Mobile Domain (PMD) family and is strongly upregulated during floral induction in response to the presence of the florigens Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1). Although OsMAIL1 expression depends on the florigens, osmail1 null mutants do not show delay in flowering time, rather OsMAIL1 participates in ensuring successful reproduction. Indeed, when day temperatures reach 35°C (7°C higher than standard greenhouse conditions), osmail1 mutants show increased sterility due to abnormal pistil development with about half of the plants developing three styles topped by stigmas. OsMAIL1 expression correlates with that of carpel identity genes and RNA-seq of osmail1-1 mutant compared to the wt during inflorescence development showed that OsMAIL1 is required to activate carpel identity genes expression when floral meristems are about to be initiated. OsMAIL1 is a newly characterized rice gene that specifically controls carpel development under heat stress, ensuring plant female fertility in these conditions

overall_design: Transcriptome comparison between wild type and osmail1-1 rice plants, at two different timepoints (15SDs and 21SDs after induction)


title: The effect of expressing dephosphorylated GYS on MSCs

city: Beijing

first: Xu

last: Yongyue

state: Beijing

address: Tsinghua University

institute: Tsinghua University

summary: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine, including the treatment of pulmonary fibrosis. However, implanted MSCs disappear within days, constraining therapeutic efficacy, which is largely attributed to nutrient deprivation. In this study, we established glycogen metabolism engineering strategies in mammalian cells. By expressing a functionally optimized glycogen synthase (GYSmut), MSCs could accumulate large amounts of glycogen rapidly as a reserve substance. We performed RNA-seq on engineered MSCs to understand its effects.

overall_design: MSCs were transduced with lentivirus expressing mutated dephosphorylated GYS1 (GYSmut group), while MSCs of the control group expressed GFP.

first: Yongyue

last: Xu

first: Mamatali

last: Rahman

first: Zhaoyan

last: Wang

first: Qiong

last: Wu


title: IGF2BP3 Inhibits Translation in Round Spermatozoa

city: Guangzhou

first: Zhenyi

last: Huang

state: GuangDong

address: ShaTaiNan Street 1023-1063,Baiyun

department: Development

institute: Southern Medical University

summary: To reveal the effects of IGF2BP3 on mouse spermatids at the post-transcriptional and translational levels, we performed RNA-seq and ribosome nascent-chain complex sequencing (RNC-seq) of spermatids from Igf2bp3+/- and Igf2bp3-/- mice after isolation. RNA-seq and RNC-seq sequencing showed that IGF2BP3 mainly plays a regulatory role in translational repression in spermatids.

overall_design: RNA-seq and RNC-seq of spermatids from Igf2bp3+/- and Igf2bp3-/- mouse testes by flow sorting. Three biological replicates per sample.

first: D

middle: Z

first: J

middle: X

last: Zhao

first: Y

last: Zhou

first: Z


title: Nucleus Accumbens MEF2C Mediates the Maintenance of Peripheral Nerve Injury-induced Physiological and Behavioral Maladaptations

city: New York

first: Molly

last: Estill

state: NY

address: 1 Gustave L. Levy Place

department: Neuroscience

institute: Mount Sinai School of Medicine

summary: Pre-clinical and clinical work has demonstrated altered plasticity and activity in the nucleus accumbens (NAc) under chronic pain states, highlighting critical therapeutic avenues for the management of chronic pain conditions. In this study, we demonstrate that myocyte enhancer factor 2C (MEF2C), a master regulator of neuronal activity and plasticity, is repressed in NAc neurons after prolonged spared nerve injury (SNI). Viral-mediated overexpression of Mef2c in NAc neurons partially ameliorated sensory hypersensitivity and emotional behaviors in mice with SNI, while also altering transcriptional pathways associated with synaptic signaling. Mef2c overexpression also reversed SNI-induced neuronal hyperexcitability and sensitized dopamine release after phasic stimulation. Transcriptional changes induced by Mef2c overexpression were different than those observed after desipramine treatment, suggesting a mechanism of action different from antidepressants. Overall, we show that interventions in MEF2C-regulated mechanisms in the NAc are sufficient to disrupt the maintenance of chronic pain states, providing potential new treatment avenues for neuropathic pain.

overall_design: C57BL/6J or DBA/2J mice (8-9 weeks old) were obtained from Jackson Laboratories and maintained on a 12-hour light/dark cycle with ad libitum access to food and water. Tibial SNI was performed on the left sciatic nerve under inhaled isoflurane. In Sham-operated mice, the same procedure was followed, but the nerves were left untouched. Stereotaxic coordinates for bilateral viral vector injections into the NAc were as follows with respect to bregma: AP, +1.60mm; ML: ±1.50mm; DV, -4.40mm at an angle of 10° from the midline. AAV8-hSyn-Mef2c-Egfp and AAV8-hSyn-Egfp were supplied by the Akbarian Lab at the Icahn School of Medicine at Mount Sinai. Approximately 7x10^9 viral particles were administered into the NAc of each hemisphere.

first: Randal

last: Serafini

first: Zahra

last: Farzinpour

first: Vishwendra

last: Patel

first: Abigail

last: Kelley

first: Kerri

last: Pryce

first: Farhana

last: Sakloth

first: Collin

last: Teague

first: Angelica

last: Torres-Berrio

first: Eric

middle: J

last: Nestler

first: Li

last: Shen

first: Schahram

last: Akbarian

first: Anushree

last: Karkhanis

first: Robert

last: Blitzer

first: Venetia

last: Zachariou


title: A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure

first: Ivan

last: Moskowitz

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

overall_design: Refer to individual Series


title: Gene expression comparison between human glioma cells: U87-MG wild-type and CHI3L1 knock-out (clone 1 and 2)

city: Warsaw

first: Bartosz

last: Wojtas

address: Pasteura 3

country: Poland

institute: Nencki Institute of Experimental Biology

summary: U87-MG human glioma cells were subjected to CRISPR/Cas9 genetic engineering to knock-out CHI3L1 gene. We then compared gene expression profiles between maternal cells (wild-type, WT) and two clones obtained throught CRISPR/Cas9 pipeline: clone 1 (KO1) and clone 2 (KO2)

overall_design: We extracted RNA from 3 subsequent cell culture passages after 48h of growth (n=3 for each condition: WT, KO1 and KO2). We assessed the quality of extracted RNA for an RIN of >9. We prepared libraries with KAPA Stranded mRNA-Seq Kit (Roche) and then performed pair-end sequencing: 2x 76 cycles, target number of reads: 25 million per sample on Illumina HiSeq 1500.

first: Salwador

last: Cyranowski

first: Bartłomiej

last: Gielniewski

first: Paulina

last: Szadkowska

first: Bozena

last: Kaminska


title: Pseudopaline-mediated zinc uptake by Pseudomonas aeruginosa drives clinically relevant phenotypes and infection outcomes

status: Public on Nov 28 2025

city: Braunschweig

first: Nicolas

middle: Oswaldo

last: GOMEZ

state: Lower Saxony

address: Inhoffenstraße 7

institute: Helmholtz Center for Infection Research

summary: Biological metals are vital trace elements required by metalloproteins, which are involved in virtually every cellular, structural and catalytic function of the bacterial cell. Bacterial pathogenesis involves a tug-of-war between the host’s nutritional immunity sequestering essential metals and the invading pathogens that deploy adapted high-metal affinity uptake strategies such as metallophores, in order to efficiently circumvent these defence mechanisms. Pseudopaline is a metallophore produced and secreted by Pseudomonas aeruginosa to acquire zinc when the bioavailability of this metal is severely restricted, as in the presence of a strong metal chelator such as EDTA, or during infections when the nutritional immunity of the host is active. We show that when facing strong metal chelation, the general Znu zinc uptake pathway becomes ineffective and only the pseudopaline pathway is capable of supplying the bacteria with the necessary zinc to maintain their growth, establishing that the pseudopaline pathway is the last-resort pathway for the bacteria to acquire zinc under such restricted growth conditions. Based on this statement, the present study explores the pleiotropic role of pseudopaline-mediated zinc acquisition on clinically relevant phenotypes such as biofilm formation and associated antibiotic tolerance, as well as its capacity to determine infection outcomes using cell-culture and murine models. The expression of pseudopaline-dependent phenotypes in such a diversity of biological contexts demonstrates the essentiality of this specific metal uptake system for P. aeruginosa pathogenicity during infection. We therefore identify this machinery as a promising therapeutic target for P. aeruginosa’s infections.

overall_design: Pseudomonas aeruginosa UCBPP-PA14 mutant strains were planktonically cultured in MCM media for 10h (RNA seq experiment).

first: Lola

last: Bosc

first: Thomas

last: Sécher

first: Geneviève

last: Ball

first: Deborah

last: Le Pennec

first: Mathilde

last: Tribout

first: Moly

last: Ba

first: Yingjie

last: Bai

first: Laurent

last: Ouerdane

first: Erdmann

last: Jelena

first: Pascal

last: Arnoux

first: Yann

last: Denis

first: Xiaoguang

last: Lei

first: Christophe

last: Bordi

first: Nathalie

last: Heuzé-Vourc’h

first: Susanne

last: Häussler

middle: O

last: Gomez

first: Romé

last: Voulhoux


title: A Natural Cyclic Peptide Enhances Cytotoxic Th9 Differentiation and Antitumor Immunity (ATACseq)

first: yang

last: zhou

address: South Shatai Road, Baiyun District

summary: Adoptive cell therapy (ACT) relies on durable and functional T cells to mediate tumor clearance. Th9 cells are a metabolically fit CD4⁺ T cell subset with strong persistence but limited cytotoxicity. Here, we identify Endomelipaneptide A (EpA), a cyclic peptide from Ganoderma lucidum–associated endophytic fungi, as a potent enhancer of Th9 differentiation. EpA promotes a cytotoxic Th9 phenotype with enhanced mitochondrial function and metabolic fitness.

overall_design: Naïve CD4+ T cells were isolated from splenocytes of C57BL/6J, and were cultured in RPMI 1640 medium containing 10% FBS, 1% penicillin-streptomycin and 0.1% β-Mercaptoethanol. Naïve CD4+ T cells were differentiated under plate-bound anti-CD3 (Bioxcell, 17A2, 5 μg/mL) and soluble anti-CD28 (Bioxcell, 37.51, 1 μg/mL) conditions with specific cytokines for Th9 differentiation: IL-4 (peprotech 400-04,10 ng/mL), TGF-β (EPOTO Biotech, 1 ng/mL), anti-IL-12 (Bioxcell, C17.8, 5 μg/mL), and anti-IFN-γ mAbs (Bioxcell, XMG1.2, 10 μg/mL). After the initial 3-day culture, cells were continue culture: IL-4 (10 ng/mL), TGF-β (1ng/mL). Th9 cells on day 4 were analyzed by ATACseq.

first: Wenli

last: Zhao

first: Yang

last: Zhou

first: Yuyang

last: Chen

first: Enguang

last: Bi


title: Vascular endothelial IRE1α promotes thrombospondin-1 mRNA decay and supports the functional adaptation of pancreatic islets upon metabolic stress

status: Public on Nov 29 2025

first: Xiaoge

last: Zhang

state: Hubei

address: BAYI road

institute: wuhan university

summary: It remains unknown whether ER stress response signaling has a metabolic regulatory role in ECs. Here, in mice with high-fat diet-induced obesity, we found that EC-specific ablation of IRE1α selectively impaired the compensatory adaptation of pancreatic islet function in response to metabolic stress. Loss of IRE1α in ECs resulted in significantly lower intra-islet angiogenesis, accompanied by defects in the compensatory growth of pancreatic islets and their capacity of glucose-stimulated insulin secretion, consequently leading to hyperglycemia. Mechanistically, IRE1α could downregulate the intra-islet EC expression of the mRNA encoding thrombospondin-1 (THBS1/TSP1), an endogenous anti-angiogenic factor implicated in islet function regulation and prediabetes, through its RIDD activity. Importantly, EC-specific depletion of THBS1 completely corrected these islet dysfunctions arising from IRE1α deficiency in ECs. Together, our findings demonstrate a critical role of the endothelial IRE1α suppression of THBS1 in governing the vascular support that enables the homeostatic adaptation of pancreatic islets to cope with overnutrition-associated metabolic stress.

overall_design: To investigate the physiological functions of IRE1α in endothelial cells under the challenge of excess nutrition, we generated endothelial cell IRE1α deletion strain and established a high fat diet (HFD)-induced obesity model. We intercrossed floxed IRE1α (Ern1fl/fl) mice with the VE-cadherin-CreERT2 line to create vascular endothelial cell-specific IRE1α-knockout (Ern1EC-KO) mice by a tamoxifen (Tam)-inducible system.To explore how IRE1α promotes intra-islets angiogenesis, we performed bulk RNA-seq transcriptome analysis of islets from Ern1fl/fl and Ern1EC-KO mice after 16-weeks HFD feeding.

first: Shijia

last: Huang

first: Yong

last: Liu


title: A Natural Cyclic Peptide Enhances Cytotoxic Th9 Differentiation and Antitumor Immunity

overall_design: Naïve CD4+ T cells were isolated from splenocytes of C57BL/6J, and were cultured in RPMI 1640 medium containing 10% FBS, 1% penicillin-streptomycin and 0.1% β-Mercaptoethanol. Naïve CD4+ T cells were differentiated under plate-bound anti-CD3 (Bioxcell, 17A2, 5 μg/mL) and soluble anti-CD28 (Bioxcell, 37.51, 1 μg/mL) conditions with specific cytokines for Th9 differentiation: IL-4 (peprotech 400-04,10 ng/mL), TGF-β (EPOTO Biotech, 1 ng/mL), anti-IL-12 (Bioxcell, C17.8, 5 μg/mL), and anti-IFN-γ mAbs (Bioxcell, XMG1.2, 10 μg/mL). After the initial 3-day culture, cells were continue culture: IL-4 (10 ng/mL), TGF-β (1ng/mL). RNAex Pro RNA Reagent was used to obtain total RNA of Th9 cells on day 4 for RNAseq.


title: amplicon sequence analysis of iPSC-derived iNKT cells and primary iNKT cells

city: Kyoto

first: Shin

last: Kaneko

state: Kyoto

address: 53 shogoin Kawaharacho Sakyo-ku

country: Japan

institute: Kyoto University

summary: 20282 gene expressions of iPSC-derived iNKT cells and primary iNKT cells  were acquired by amplicon-seq and compared their gene expression similarity

overall_design: Examination of mRNA expression from iPSC-derived iNKT cells differentiated using 2D or 3D culture methods and primary iNKT cells

first: Sara

last: Shiina

first: Tatsuki

last: Ueda

first: Shoichi

last: Iriguchi

first: Yasushi

last: Uemura


title: Tbr2-dependent parallel pathways regulate the development of distinct ipRGC subtypes

city: Houston

first: Chai-An

last: Mao

state: Texas

address: 6431 Fannin Street, MSB7.242

department: Ophthalmology And Visual Scien

institute: University of Texas McGovern Medical School

summary: The intrinsically photosensitive retinal ganglion cells (ipRGC) are the conduit between the retina and brain regions responsible for non-image-forming and image-forming vision. In mice, six ipRGC subtypes have been discovered based on morphological characteristics, functions, and molecular profiles. All ipRGCs arise from Tbr2-expressing RGCs during developmental stages and subsequently diverge and differentiate into the six mature, distinct subtypes in adult retinas. However, the cellular and molecular mechanisms controlling the formation and maturation of the six ipRGC subtypes remain elusive. Here, we demonstrate that two Tbr2-dependent transcription factors, Iroquois‑related homeobox 1 (Irx1) and T-box containing factor 20 (Tbx20), are key downstream transcription factors guiding lineage segregations of Tbr2-expressing RGC into distinct adult ipRGC subtypes. Both factors also control Opn4 expression. Irx1 is expressed in the M3, M4, and M5 subtypes, while Tbx20 is predominantly expressed in M1, M2, M6, and subgroups of M3 and M5. When Irx1 is ablated during retinal development, Opn4 expression is significantly reduced in the M3, M4, and M5 ipRGC groups; however, the formation of Irx1-expressing ipRGCs is not affected. In contrast, when Tbx20 is deleted, a significant number of Tbx20-expressing cells fail to develop while Opn4 expression is down-regulated. These findings reveal two parallel transcription cascades downstream of Tbr2 for controlling ipRGC subtype formation, fate divergence, and maintenance in the adult retina.

overall_design: Twelve retinas from E15.5 wildtype and Tbr2f/f;Six3-Cre embryos from multiple litters were pooled and RNA were extracted using RNAeasy mini kit (QIAGEN). Bulk RNA sequencing were performed in Novogene. Sequencing library were prepared using standard Illumina protocol. RNA sequencing were performed using Illumina HiSeq 6000. Illumina Casava was used for basecalling. The RNA-seq reads were mapped to the mouse genome (mm10) via STAR (v2.5). HTSeq (v0.6.1) was used to count the read numbers mapped to each gene. Differential expression analysis of two groups was performed using the DESeq2 R package (v2_1.6.3). The resulting P-values were adjusted using the Benjamini and Hochberg’s approach for controlling the false discovery rate. Genes with an adjusted P-value<0.05 were considered as differentially expressed.

first: Takae

last: Kiyama


title: A reduced TBX5-dependent gene regulatory network links atrial fibrillation and heart failure [RNA-seq: Tbx5_LV_KO]

first: Ivan

last: Moskowitz

first: Sonja

last: Lazarevic

first: Carlos

last: Perez-Cervantes


title: Chromatin Accessibility and Gene Expression Dynamics Suggest Immune-Modulatory Effects of Vitamin D3 In Vivo [ATAC-seq]

city: Olsztyn

first: Maciej

last: Rybiński

state: Warmian-Masurian Voivodeship

address: Trylińskiego 18

institute: Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences.

summary: Vitamin D3 is a key micronutrient known to support innate immunity and modulate adaptive responses, with in vitro studies suggesting involvement of epigenetic mechanisms. However, in vivo evidence for such regulation remains limited. In this proof-of-principle study, we investigated genome-wide epigenomic and transcriptomic responses to vitamin D₃ in a high responder (n=1) from the VitDHiD intervention trial. The participant received monthly oral boluses of 80,000 IU vitamin D3 over three months. Peripheral blood mononuclear cells were collected at baseline (day 0) and at 24 and 48 hours post-supplementation (days 1 and 2) for ATAC-seq and RNA-seq profiling. ATAC-seq revealed over 3,500 regions with increased chromatin accessibility, mainly at gene promoters, indicating a strong epigenomic response. Motif enrichment analysis identified immune-regulatory transcription factors, but not VDR (vitamin D receptor) motifs, suggesting indirect or cooperative regulation. RNA-seq identified 380 vitamin D target genes with time-dependent expression changes, including DUSP6 and FOS. Functional enrichment highlighted pathways related to innate immunity and interferon signaling. Integrative analysis linked 306 differentially expressed genes to nearby vitamin D-sensitive chromatin regions, including both promoters and enhancers. Many of these overlapped with VDR binding sites and promoters of neighboring non-target genes, indicating potential long-range regulatory interactions. Redundancies in regulatory elements were observed among closely located genes sharing enhancers and promoters. These findings provide in vivo evidence that vitamin D3 modulates chromatin accessibility and gene expression, supporting its role as an epigenetic regulator of immune function and highlighting its potential in personalized nutrition and immune health.

overall_design: ATAC-seq libraries of PBMCs obtained from a healthy individual before (day 0) as well as 24 hour (day 1) and 48 hours (day 2) after taking a vitamin D3 bolus (80.000 IU) in three biological repeats

first: Rybiński

last: Maciej

first: Carlberg

last: Carsten


title: Splice isoform-perturbation coupled to single cell transcriptome profiling reveals functions of microexons in neurogenesis and autism-linked pathways [RNA-seq]

city: Toronto

first: Steven

last: Dupas

address: 160 College St.

institute: University of Toronto

summary: A major challenge of biomedical research is to assign functions to the myriad alternative RNA and protein isoforms. This challenge is particularly relevant to the mammalian nervous system, which produces complex repertoires of alternative splicing events. Here, we describe CHyMErA-seq, a platform that couples systematic deletion of exons to a single cell transcriptomics read-out, and apply this method to investigate a critical program of brain-specific microexons. Perturbation of microexons during neurogenesis reveals convergent roles in the temporal regulation of gene expression programs that direct signalling pathways and morphogenesis. We further observe microexons, including those in the Bin1, Clasp1, Gfra1, Med23, Ptprf and Ralgapb genes, that are required for the correct timing of autism-linked gene expression. Collectively, we describe a flexible system for isoform-resolution perturbation at a single cell level, together with insights into the roles of microexons in the developmental timing of neurogenesis transcriptomic signatures linked to brain disorders.

overall_design: RNA-seq of mouse embryonic stem cells and in vitro differentiated neurons for dCasRx-RBM25 mediated exclusion or exclusion of a target exon in Camta1, Clasp, Ptk2 or Ptprf in duplicate, or Cas9 mediated deletion of Gfra1 homozygous deletion clones or wild type clonal cell lines.

first: Guillermo

last: Parada

first: Jack

last: Diayang Li

first: Kevin

last: Brown

first: Jason

last: Moffat

first: Benjamin

last: Blencowe


title: IPSC-Derived CAR-NK Extracellular Vesicles Remodel Macrophage Immunity and Enhance Tumor Eradication

status: Public on Nov 26 2025

first: Hao

last: Zhang

address: 1101 E. 58th Street, Chicago

institute: University of Chicago

summary: Chimeric antigen receptor (CAR) cell therapy has revolutionized the treatment of hematological malignancies; however, its efficacy in solid tumors remains limited due to dense stromal barriers and the immunosuppressive tumor microenvironment (TME), which hinder immune cell infiltration and persistence. To overcome these challenges, we propose an innovative strategy utilizing induced pluripotent stem cell (iPSC)-derived CAR-NK extracellular vesicles (CAR-iNEV), engineered from iPSC-differentiated NK cells. Unlike conventional CAR-NK cell therapies that rely on immortalized NK92 cell lines, our approach leverages iPSC-derived NK cells, reducing tumorigenic risk and enhancing CAR transduction efficiency. Additionally, we incorporate nanobody-based CAR constructs in place of traditional single-chain variable fragments (scFv), significantly improving CAR stability and expression efficiency. Beyond direct cytotoxicity, CAR-iNEV offers superior therapeutic advantages, including reduced systemic toxicity and enhanced drug delivery capabilities compared to CAR-iNK cells. In vivo studies demonstrate that CAR-iNEV exhibits exceptional safety and potent antitumor activity across multiple solid tumor xenograft and patient-derived xenograft (PDX) models in humanized mice. Mechanistically, CAR-iNEV not only directly eliminates tumor cells but also reprograms the TME by activating macrophage-derived nitric oxide synthase (NOS2), amplifying host antitumor immunity. These findings establish CAR-iNEV as a promising platform for solid tumor immunotherapy, particularly in relapsed and metastatic settings, providing a novel and effective strategy that bridges direct tumor targeting with immune microenvironment remodeling. This study lays the foundation for future clinical translation, advancing the next generation of cell-free CAR-based immunotherapies.

overall_design: To further elucidate the impact of CARCD133-iNEV on the TME, we performed single-cell RNA sequencing (scRNA-seq) on CD45⁺ immune cells isolated from tumor tissues collected two weeks post-treatment. Preliminary analysis revealed significant alterations in the composition of tumor-infiltrating immune cell subsets in the CARCD133-iNEV treatment group, suggesting a profound reprogramming effect on immune cells

first: Peng

last: Xia

first: Bin

last: Jin

first: Minghe

first: Jie

last: Liu


title: EGFR-mutant transformed small cell lung cancer harbors intratumoral heterogeneity targetable with MEK inhibitor combination therapy

status: Public on Nov 25 2025

city: Boston

first: Zhaorong

last: Li

address: 60 Fenwood Road

institute: Dana Farber Cancer Institute

type: Genome variation profiling by high throughput sequencing

summary: Small cell lung cancer (SCLC) transformation is an incompletely characterized mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant cancers, limiting development of optimal treatment approaches. Through single-cell RNA sequencing of malignant pleural effusions from patients who underwent SCLC transformation, we identified heterogeneity and diversity including distinct neuroendocrine (NE) and mesenchymal non-NE cancer cell subsets, which was maintained in patient-derived cell lines. We demonstrate that EZH2 regulates EGFR expression in NE cells where EGFR expression is silenced at baseline. Although neither epigenetic derepression nor exogenous overexpression of mutant EGFR sensitized the cells to EGFR inhibition, non-NE cells exhibited selective sensitivity to MEK inhibitors. Combined MEK inhibitor and chemotherapy effectively inhibited growth of both NE and non-NE cells in vitro and in vivo. Our findings demonstrate that EGFR mutant SCLC is composed of mixed cell states with distinct therapeutic vulnerabilities and offer a novel therapeutic strategy to target tumor heterogeneity in highly plastic and treatment-resistant malignancies such as SCLC transformed cancers.

overall_design: 4 Whole exome sequencing samples and 3 single cell RNA-Seq samples were generated from small cell lung cancer patient derived model

first: Ogino

last: Atsuko

first: Book

last: Matthew

first: Tolstorukov

last: Michael

first: Jänne

last: Pasi

first: Barbie

last: Dave

first: Oser

first: Paweletz

last: Cloud

first: Gokhale

last: Prafulla


title: Mesothelioma location influences the tumour microenvironment and immune checkpoint therapy response in preclinical models

city: Crawley

first: M. Lizeth

last: Orozco Morales

state: WA

address: 35 Stirling Hwy

country: Australia

institute: University of Western Australia

summary: Mesothelioma is a cancer derived from mesothelial cells, most commonly arising from the pleura or the peritoneum. Immune checkpoint therapy (ICT) has shown survival benefit for pleural mesothelioma, but little is known about the response in peritoneal mesothelioma. Most preclinical mesothelioma models involve subcutaneous cancer cell implantation, which lacks the relevant tumour microenvironment of peritoneal mesothelioma and does not resemble the clinical presentation. We therefore set out to explore the influence of location on the mesothelioma tumour microenvironment, comparing pleural, peritoneal, and subcutaneous models using identical cell line-derived syngeneic mesotheliomas. We found that the peritoneal location conferred an anti-inflammatory tumour microenvironment, characterised by low IFN, TNFα, and STAT signalling activity, low immune cell infiltration and a gene signature associated with non-response to ICT. ICT was effective in subcutaneous models, but the same cell line-derived tumours were irresponsive when inoculated intraperitoneally. Together, these findings show that peritoneal location is associated with an immune suppressive tumour microenvironment.

overall_design: RNA-seq profiling of AB1-mCherry mesothelioma tumours (whole tumours and CD45-mCherry+ sorted cancer cells) implanted in three different anatomical locations: pleural, peritoneal, and subcutaneos space, at day 10 after tumour inoculation

first: Mariana Lizeth

first: Sally

middle: M

last: Lansley

first: Wee Loong

last: Chin

first: Caitlin

last: Tilsed

first: Nicola

last: Principe

first: Connull

last: Leslie

first: Breana

last: Vitali

first: Francois

last: Rwandamuriye

first: Emma

last: de Jong

first: Joel

last: Kidman

first: Rachael

last: Zemek

first: Catherine

middle: A

last: Rinaldi

first: Timo

last: Lassmann

first: Anthony

last: Bosco

first: Y C Gary

last: Lee

first: Richard

last: Lake

first: Jonathan

last: Chee

first: Willem Joost

last: Lesterhuis


title: Chronobiology of Neurotropic Viruses: Rhythmic Viral Entry and Arrhythmic Host Clocks

city: 武汉市

first: Shaowei

last: Zeng

state: 湖北省

address: 水果湖街道

summary: Neurotropic viruses invade neural tissues, resulting in severe diseases such as poliomyelitis, rabies, herpesviral encephalitis, and viral meningitis. Given this neurotropism, we investigated whether the infection of the host by these viruses is under circadian control. Here we show that the expression of most neurotropic virus receptors exhibits rhythmicity across cells, cerebral organoids, and animal models, with host cell susceptibility modulated by the circadian clock. We identify E2F8 as a clock-controlled gene that mediates the indirect regulation of the circadian clock on neurotropic viruses. Notably, E2F8 regulates the expression of core clock components by binding directly to the promoters of REV-ERBα and PER2, suggesting its role as a potential modulator of circadian rhythms. Additionally, we uncovered a seldom-recognized viral strategy to accelerate its own replication in the host: rabies virus disrupts the host circadian clock system primarily through its glycoprotein hijacks the E3 ubiquitin ligase HUWE1 to inhibit proteasomal degradation of REV-ERBα. These findings enhance our understanding of circadian systems' interaction with neurotropic viral dynamics and highlight chronotherapy's potential for improved antiviral treatments.

overall_design: CUT&Tag-seq of BMAL1 in Cerebral organoids synchronized with 100 nM hydrocortisone at CT7

first: Qian

last: Zhang

first: Bishi

last: Fu


title: snRNA-seq dataset of 17 treatment-naive human PDAC patient-derived tumors

first: Julian

last: Frädrich

address: Ismaninger Strasse 22

department: Institute of Experimental Oncology & Therapy Research

institute: TUM School of Medicine and Health

summary: This is a human single nucleus RNA sequencing (snRNAseq) dataset of human primary pancreatic ductal adenocarcinoma (PDAC) tumor tissues of 17 (deidentified) treatment-naive patients. The goal of this study was to thoroughly characterize the tumor microenvironment in human primary PDAC.

overall_design: single-nucleus RNA-seq (snRNA-seq) profiling of human PDAC patient-derived primary tumors using the 10xGenomics Chromium Next GEM Single Cell 3’ Kit v3.1.

first: Achim

last: Krüger

first: Carmen

last: Mota Reyes

first: Ihsan Ekin

last: Demir


title: YAP1 dysfunction promotes molecular properties linked to breast cancer susceptibility

city: Stockton

first: Tara

last: Fresques

address: 3601 Pacific Ave.

department: Biology

institute: University of the Pacific

summary: YAP1 is a co-transcription factor that promotes malignant and stem cell properties in cancer. We previously found that YAP1 dysregulation is associated with aging in human mammary epithelia. With increased age, YAP1 expression changes in luminal epithelial cells, the prospective breast cancer cell of origin. Because age is a significant risk factor for breast cancer, we tested if YAP1 dysregulation acted early in cancer progression by conferring cellular states associated with increased cancer susceptibility. Here we find, that with increased age and genetic risk for developing cancer, human breast tissues showed significantly increased YAP1 expression and cultured primary human mammary epithelial cells (HMEC) showed significantly increased expression of both YAP1 and its transcriptional targets. Increased YAP1 expression in cultured HMEC induced gene expression changes associated with increased cancer susceptibility such as genes associated with: a stem cell fate, cells with increased telomerase activity, breast cancer progression, and increased age and genetic breast cancer risk. Further, overexpression of YAP1 in post-stasis HMEC- finite lifespan cells which have bypassed a retinoblastoma-mediated senescence barrier- promoted properties related to an increased growth potential. We found that YAP1 dysregulation in finite post-stasis epithelial cells allows for access to gene programs and functions that are typically thought to be restricted to stem cells. We hypothesize that YAP1 acts early in breast cancer progression, before development of a tumor, to impose cancer susceptible molecular states.

overall_design: General experimental design: Post-stasis human mammary epithelial cells (HMEC) were cultured in tissue culture plastic in M87A media. YAP1 or control constructs were transduced into cells to determine the effect of YAP1 on post-stasis HMEC. In some samples, MYC was further added to induce immortalization. In some samples, clonal immortalization events occurred. Cells were collected at different passages during post-stasis and immortal growth. Experiments were done with 2 different biological specimens: 184D and 240LB. Biological Replicate 1: Specimen 240LB. Cells were transduced with p16sh to make cells post-stasis. Control post-stasis cells were collected at passage 11. YAP1 was transduced into cells at passage 10 and cells were collected at passage 12. YAP1 transduced cultures underwent clonal immortalization around passage 18 when they were collected. Fully immortal YAP1 transduced cells were collected at passage 25. Biological Replicate 2: Specimen 240LB. Cells were transduced with p16sh to make cells post-stasis. YAP1 or control virus was transduced into cells at passage 10 and cells were collected at passage 12. YAP1 transduced cultures underwent clonal immortalization around passage 16 when they were collected. Fully immortal YAP1 transduced cells were collected at passage 22. Biological Replicate 3 (All samples collected in triplicate): Specimen 184D. Cells were transduced with p16sh to make cells post-stasis. YAP1 or control virus was transduced into cells at passage 10 and cells were collected at passage 12. Control cells approached replicative senescence at passage 18; control and YAP1 transduced cells were collected at passage 17. YAP1 transduced cultures underwent rare immortalization event(s) around passage 18 when they were collected. Fully immortal YAP1 transduced cells were collected at passages 20 and 24. Control and YAP1 post-stasis cells were also transduced with MYC at passage 12 and immortalized cells were collected at passages 15 and 21.

first: Debbie

last: Hussey

first: Jennifer

last: Lopez

first: Masaru

last: Miyano

first: James

last: Garbe

first: Stefan

last: Hinz

first: Rosalyn

last: Sayaman

first: Aimin

last: Li

first: Serenity

last: Van Bedford

first: Daniel

last: Schmolze

first: Martha

last: Stampfer

first: Mark

last: LaBarge


title: Pancreatic gene expression patterns during PDAC development in mice

summary: This is a bulk RNA sequencing dataset of pancreatic tumors of varying disease grades from genetically engineered PDAC-bearing KPC mice (Pdx-1+/Cre; Kras+/LSL-G12D; Trp53+/LSL-R172H) (n = 24), and healthy controls (n = 11). KPC-derived tissues comprised early PDAC (only pancreatic remodeling and/or preinvasive lesions) to advanced disease (PDAC grades 2, 3, and 4). Mice resulting from KPC strain breeding, which did not carry Pdx-1+/Cre but only Kras+/LSL-G12D and/or Trp53+/LSL-R172H-mutations, or which carried no mutation at all, served as control animals. To identify the changes in pancreatic gene expression during PDAC development, bulk RNAseq was performed on harvested pancreatic tissues.

overall_design: Total RNA was isolated from banked frozen pancreatic tissues using the RNeasy Plus Mini Kit (Qiagen) and RNAseq was performed on a NovaSeq X Plus platform (Illumina).


title: Splice isoform-perturbation coupled to single cell transcriptome profiling reveals functions of microexons in neurogenesis and autism-linked pathways [snRNA-Seq]

first: Steven

last: Dupas

overall_design: Single-nuclear expression profiling of pooled CRISPR screen for deletion of conserved alternative exons.

first: Guillermo

last: Parada

first: Jack

last: Diayang Li

first: Kevin

last: Brown

first: Jason

last: Moffat

first: Benjamin

last: Blencowe


title: Rapid clearance of bacteria from maternal bloodstream after delivery in pregnancies complicated by pre-labor premature rupture of the membranes.

status: Public on Nov 27 2025

city: Chicago

first: William

last: Ackerman

state: Illinois

address: 820 South Wood Street, MC 808, Dept. of Obstetrics & Gynecology

department: Obstetrics and Gynecology

institute: University of Illinois Chicago College of Medicine

summary: Objective: We investigated whether birth in patients whose pregnancies are complicated by pre-labor premature rupture of the membranes (PPROM) is associated with translocation of microbes in maternal circulation and a systemic inflammatory process. Research Design and Methods: 66 pregnant patients admitted for PPROM [gestational age (GA) median [IQR]: 32±1 weeks] had maternal blood (MB) retrieved prior to birth and within 1-hour post-partum. Immediately after birth, fetal membranes (FM) and placental tissue were frozen in sterile fashion. Bacterial load was assessed by 16S rDNA gene amplification by qPCR. Multiplexed 16S amplicon libraries were sequenced on the Illumina platform and enrichment analysis performed using LfSe and EdgeR. Pro- and anti-inflammatory cytokines were measured in MB using multiplex immunoassay. Histological chorioamnionitis (HCA) and cord blood haptoglobin and IL-6 indicated fetal exposure to antenatal inflammation (Triple I). Results: Bacterial DNA was identified in MB both before and after birth. A significant decrease in MB bacterial DNA was observed within 1-hour post-delivery (p=0.004). Conversely, MB cytokines IL-6 and Il-10 increased significantly (p<0.05 for all) especially in pregnancies exposed to Triple I. Compared to placenta, FM carried a higher bacterial load (p<0.001) regardless of presence or absence of antenatal inflammation. FM had higher bacterial biodiversity with top representation from Mycoplasma spp although Mycoplasma was not found in MB either pre- or post-delivery. While no taxa were systematically enriched in MB post-delivery, sample-by-sample analysis identified three cases where a MB OTU had a match in FM and four cases with a match in placenta. Yet, the most abundant MB OTUs had no match in either tissues. Conclusion: In patients with PPROM, bacterial DNA is present in MB prior to birth but is rapidly removed after delivery in association with a robust immediate postpartum cytokine surge.

sample_organism:
human metagenome
human blood metagenome

platform_organism:
human metagenome
human blood metagenome

overall_design: Using a prospective observational study design, we enrolled 66 consecutive pregnant patients who were admitted on the antepartum service of our academic university hospital for management of pre-labor premature rupture of the membranes (PPROM) at ≤34 weeks gestational age (GA). Subjects were eligible for enrollment if older than 18 years of age, pregnant between 230/7 to 336/7 weeks gestational age and at high risk of preterm birth secondary to PPROM. Exclusion criteria were anticipated delivery within 2 hours, need for close medical supervision (e.g. cardiac and renal disease, congestive heart failure, history of asthma), maternal viral infection (HIV, hepatitis B or C), known active infections or antibiotic use 7 days prior to admission, need for emergent delivery (e.g. cord prolapse, abruption) and known fetal malformations. Maternal blood (MB) was retrieved via sterile venous puncture prior to birth and within 1-hour post-partum (PP). An alcohol swab was used to prepare the skin area before venipuncture. The blood was collected in serum and plasma citrate tubes (BD Vacutainer, Franklin Lakes, NJ) and transported to the laboratory. An aliquot of whole blood from the plasma tube was first saved for bacterial DNA isolation. The remainder blood volume was spun at 1,500 g for 15 min and plasma and serum aliquoted for cytokine measurements. Cord blood was collected at delivery from all newborns of mothers enrolled in this study. After delivery of the placenta, a loop of the umbilical cord was placed on a sterile field and cord blood was collected by sterile puncture of the umbilical vein. The cord blood was processed as described above for MB. In a subset of deliveries (n=31 newborns: 23 singletons and 4 pairs of twins), a biopsy from FM (full thickness amniochorion) and from the villous tissue in center of the placental disk were retrieved in strict sterile fashion within minutes from delivery. Collection of delivery tissues was contingent on availability of research staff at delivery. Following dissection of the decidua basalis, the villous trophoblast tissue was frozen immediately in liquid nitrogen. The fetal membrane biopsy was rinsed briefly in sterile saline to remove any AF and adherent blood prior to freezing in sterile DNA-free tubes.

first: Irina

last: Buhimschi

middle: E

first: Catalin

middle: S


title: Transcriptome-wide Identification of RNA Bound by IGF2BP3 in Mouse Testes by eCLIP-seq

first: Zhenyi

last: Huang

address: ShaTaiNan Street 1023-1063,Baiyun

summary: The knockout of IGF2BP3 affects the proper progress of spermatogenesis. We use Enhanced Crosslinking Immunoprecipitation Sequencing (eCLIP-seq) to find the targets bound by IGF2BP3 in the testis. After conducting joint analysis with the RNC-seq of knockout mice, we identified that changes in the downstream target genes of IGF2BP3 at the transcriptional and translational levels will damage the conversion of histones to protamines.

overall_design: eCLIP-seq in mouse testes with anti-IGF2BP3 or anti-IgG. Three biological replicates per sample.

first: D

last: Wang

first: Z


title: A metabolism-chromatin axis promotes ribosome heterogeneity in the human malaria parasite [II]

city: Paris

first: Sebastian

last: Baumgarten

address: 25, Rue du Dr. Roux

department: Parasites and Insect Vectors

institute: Institut Pasteur

summary: The transmission of the most virulent human malaria parasite, Plasmodium falciparum, relies on the survival in the contrasting environments of the human host and mosquito vector. One of the most fascinating adaptations to this lifestyle is the specific silencing of individual rDNA genes in the human host that are de-repressed following host-to-vector transmission. In this study, we characterized the epigenetic signatures of active and silent rDNA loci and found that rDNA silencing  relies on aerobic glycolysis, the sole energy-generating pathway in the human host. We show that disruption of NAD+ regeneration during lactate fermentation promotes rDNA de-repression and identify Sir2 as the mediator between fluctuating NAD+ levels and a functional transcriptional outcome. Hence, rDNA activation appears to be coupled to the metabolic state of the parasite as it transitions from aerobic glycolysis to mitochondrial respiration during host-to-vector transmission.

overall_design: Protein-DNA proximity labelling approach using the bacterial M.EcoGII 6mA DNA methyltransferase fused to Sir2a. Sir2a interaction with histones leads to 6mA modification of nearby adenines that are identified using direct DNA ONT sequencing

first: Justine

last: Couble

first: Tiziano

last: Vignolini

first: Gregory

last: Dore

first: Bérangère

last: Lombard

first: Michael

last: Richard

first: Damarys

last: Loew

last: Büttner

first: Rafael

last: Dueñas-Sánchez

first: Gernot

last: Poschet

first: Jessica

last: Bryant


title: A metabolism-chromatin axis promotes ribosome heterogeneity in the human malaria parasite

overall_design: ChIP sequecing of H3K9ac, H3K14ac, H4K12ac and H4K16ac in Plasmodium falciparum wild-type (strain 3D7) and Sir2a-KO parasites.

first: Couble

last: Justine

first: Vignolini

last: Tiziano

first: Dore

last: Gregory

first: Lombard

last: Bérangère

first: Richard

last: Michael

first: Loew

last: Damarys

first: Büttner

first: Dueñas-Sánchez

last: Rafael

first: Poschet

last: Gernot

first: Bryant

last: Jessica

first: Baumgarten

last: Sebastian


title: Chidamide and Anlotinib act synergistically in Jurkat cells by inhibiting the Hippo signaling pathway

status: Public on Nov 24 2025

city: luzhou

first: Tao

last: Ma

state: si chuan

address: taiping jie

department: Department of Hematology

institute: Affiliated Hospital of Southwest Medical University

summary: T-cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive hematologic malignancy characterized by drug resistance, relapse and poor prognosis. Chidamide, a histone deacetylase inhibitor, has shown epigenetic therapeutic potential in T-ALL, but its efficacy is limited and acquired drug resistance exists. To overcome these limitations, we systematically evaluated the synergistic Combination effects of three drug candidates, OTX-015 (BET inhibitor), Metformin (metabolic regulator), and Anlotinib (multitargeted tyrosine kinase inhibitor), with Chidamide.

overall_design: The human T-ALL Jurkat cell line was treated under three conditions for 48 hours: 1) Chidamide (5 μM) alone, 2) Anlotinib (1 μM) alone, and 3) Combination of Chidamide (5 μM) and Anlotinib (1 μM). Untreated cells served as control. Total RNA was extracted from biological replicates for each group and subjected to RNA sequencing (RNA-seq) on an Illumina platform with 2×150 bp paired-end reads. Differential gene expression analysis was performed to identify genes and pathways modulated by the treatments.

first: Chunli

last: Zhang


title: Cas9-mediated in vivo miRNA silencing

city: Marseille

first: Eduardo

last: GASCON

address: 27 bd Jean Moulin

institute: INT Timone

summary: Although the advent of Cas9 technology has expanded our ability to precisely edit the genome, manipulating micro RNAs in vivo has been shown to be particularly challenging, especially in the brain. Here, we sought to generate novel tools aiming at targeting and efficiently down regulating defined microRNAs species in a cell-specific manner so that their function in discrete neuronal networks could be investigated. Focusing on miR-124, a micro RNA highly expressed in the mammalian brain and transcribed from three independent chromosomal loci, we designed and validated different gRNAs directed against this miRNA. In vitro, our Cas9 designs show not only a significant reduction in miR-124 levels but also a functional effect on miR-124 silencing. Similarly, when packed into AAV vectors and injected into the mouse cortex, miR-124-Cas9 vectors strongly down regulate miR-124 levels without affecting the expression of other miRNAs. In parallel, levels of endogenous miR-124 targets exhibit a significant increase supporting the release of its silencing activity. To functionally validate our tools, we provide evidences that deletion of miR-124 in the sub ventricular zone altered migration of newly generated neurons into the olfactory bulb. Finally, we also showed that our vectors also modified the Ca2+ permeability of AMPA receptors, a robust functional output downstream of miR-124. These tools are expected to help elucidating miRNA function in complex experimental settings such as brain networks in vivo.

overall_design: The objective is to identify and quantify mutations introduced by CRISPR/Cas9 in the 3 miR-124 gene loci and the 2 miR-128 loci, as well as possible mutations introduced outside these target genes. AAVs encoding CRISPR/Cas9 were injected into the motor cortex of C57BL/6 WT mice. We tested three guides (inoperative Sa1, Sa4 targeting miR-124 and Sa2 targeting miR-128) and one construct without a guide. After 4 weeks, tissues were collected, dissociated and Cas9-positive cells were sorted by FACS.

last: Gascon

first: David

last: Roura-Martinez

first: Florence

last: Jaouen

first: Cynthia

last: Rombaut

first: Ana

last: Borges

first: Natalia

last: Popa

first: Dipankar

last: Bachar


title: Effect of knockdown of PPP2R2A on gene expreesion in NSCLC cells

city: Columbus

first: Zhaojun

last: Qiu

state: Ohio

address: 460 West 12th Ave

institute: The Ohio State University

summary: To investigate the biological roles of PPP2R2A, we conducted bulk RNA-sequencing to assess the impact of PPP2R2A knockdown using two shRNAs in two NSCLC cell lines.

overall_design: To broadly explore the signaling pathways modulated by PPP2R2A, we initially conducted an analysis of global transcriptional changes using RNA-sequencing of NSCLC A549 and H1299 cell lines. These cells were subjected to either shRNA-mediated PPP2R2A KD or a scrambled shRNA control, achieved by using two different shRNAs targeting distinct regions of PPP2R2A.

first: Junran

first: Deepika

last: Singh


title: ATAC-seq between normal skin and wound edge epidermis in Hdac5fl/fl and K14cre;Hdac5fl/fl mice

city: Shanghai

first: Yifan

address: No.639, Zhizaoju Road

department: Department of Plastic and Reconstructive Surgery

institute: Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine

summary: Re-epithelialization is a crucial process in skin wound healing.  To date, the underlying mechanisms of re-epithelialization remain elusive, and effective strategies have not yet been developed.  Histone deacetylase 5 (HDAC5), classified as a class IIa HDAC protein, primarily modulates chromatin accessibility and regulates transcriptional activity through deacetylating lysine residues on core histones.   Additionally, it engages in interactions with several transcription factors, notably the extensively researched myocyte enhancer factor 2 (MEF2), influencing the expression of MEF2-dependent genes.   Beyond histone proteins, HDAC5 has exhibited non-histone deacetylase activity, targeting substrates like tubulin and p65.   Given that the successful activation of silent genes is pivotal for an effective regeneration process, the regulatory role of HDAC5 in the transcription of genes associated with regeneration underscores its potential in wound repair.   Therefore, in this study, we investigated the differences in gene expression in the skins of hdac5 conditional knockout mice and their wild-type littermates under normal conditions and after wounding.

overall_design: To explore the influence of HDAC5 both normal skin and wound edge, we developed a model utilizing epidermal Hdac5 gene conditional knock-out K14cre;Hdac5fl/fl mice.  Employing the excisional wound splinting model, we procured the wound edge specimens for analysis.

first: Ya

last: Gao

first: Qingfeng

last: Li

first: Dongsheng

last: Wen

first: Chia-kang

last: Ho


title: Single cell RNA-sequencing reveals RNA sequencing gene expression profiles between normal skin and wound edge in Hdac5fl/fl and K14cre;Hdac5fl/fl micecellular heterogeneity and trajectories of lineage specification

overall_design: To explore the influence of HDAC5 on gene expression profiles in both normal skin and wound edge, we developed a model utilizing epidermal Hdac5 gene conditional knock-out K14cre;Hdac5fl/fl mice.   Employing the excisional wound splinting model, we procured the wound edge specimens for analysis.


title: Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility [single cell RNA-seq]

city: Newark

first: Nataki

middle: C.

last: Douglas

state: NJ

address: 185 S Orange Ave, MBS E569

department: Ob-Gyn and Women's Health

institute: Rutgers-New Jersey Medical School

summary: Embryo implantation relies on the development of a receptive endometrium during the secretory phase of the menstrual cycle. Prior studies have attempted to define the window of embryo implantation within the secretory phase based on patterns of differentially expressed genes, but consensus surrounding this signature has not been achieved.  We aim to examine the cell types that characterize the purported receptivity signature and identify new transcriptomic markers that define the mid-secretory endometrium through integrated bulk and single-cell RNA sequencing.

overall_design: Single cell transcriptome profiling of endometrial biopsies from the proliferative, early secretory, mid secretory, and late secretory menstrual phases, and decidua from the first trimester of pregnancy.

first: Gregory

middle: W

last: Burns

first: Emmanuel

middle: N

last: Paul

first: Manisha

last: Persaud

first: Qingshi

last: Zhao

first: Rong

first: Kristin

last: Blackledge

first: Jessica

last: Garcia de Paredes

first: Pratibha

last: Shukla

first: Ripla

last: Arora

first: Anat

last: Chemerinski

middle: C


title: Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility [bulk RNA-seq]

overall_design: Bulk RNA-seq profiling of endometrial biopsies from the proliferative, early secretory, mid secretory, and late secretory menstrual phases.

first: Manish


title: Chromatin Accessibility and Gene Expression Dynamics Reveal Immune-Modulatory Effects of Vitamin D3 In Vivo [RNA-Seq]

first: Maciej

last: Rybiński

summary: Vitamin D₃ is a key micronutrient known to support innate immunity and modulate adaptive responses, with in vitro studies suggesting involvement of epigenetic mechanisms. However, in vivo evidence for such regulation remains limited. In this proof-of-principle study, we investigated genome-wide epigenomic and transcriptomic responses to vitamin D₃ in a high responder (n=1) from the VitDHiD intervention trial. The participant received monthly oral boluses of 80,000 IU vitamin D₃ over three months. Peripheral blood mononuclear cells were collected at baseline (day 0) and at 24 and 48 hours post-supplementation (days 1 and 2) for ATAC-seq and RNA-seq profiling. ATAC-seq revealed over 3,500 regions with increased chromatin accessibility, mainly at gene promoters, indicating a strong epigenomic response. Motif enrichment analysis identified immune-regulatory transcription factors, but not VDR (vitamin D receptor) motifs, suggesting indirect or cooperative regulation. RNA-seq identified 380 vitamin D target genes with time-dependent expression changes, including DUSP6 and FOS. Functional enrichment highlighted pathways related to innate immunity and interferon signaling. Integrative analysis linked 306 differentially expressed genes to nearby vitamin D-sensitive chromatin regions, including both promoters and enhancers. Many of these overlapped with VDR binding sites and promoters of neighboring non-target genes, indicating potential long-range regulatory interactions. Redundancies in regulatory elements were observed among closely located genes sharing enhancers and promoters. These findings provide in vivo evidence that vitamin D₃ modulates chromatin accessibility and gene expression, supporting its role as an epigenetic regulator of immune function and highlighting its potential in personalized nutrition and immune health.

overall_design: RNA-seq libraries of PBMCs obtained from a healthy individual before (day 0) as well as 24 hour (day 1) and 48 hours (day 2) after taking a vitamin D3 bolus (80.000 IU) in three biological repeats

first: Rybiński

last: Maciej

first: Carlberg

last: Carsten


title: Intracellular traction forces modulate chromatin accessibility at the FOXO1 locus

status: Public on Nov 23 2025

city: Chengdu

first: Li

last: Liao

state: Sichuan

address: No. 24, South Section 1, First Ring Road

institute: SiChuan University

summary: In summary, our study demonstrates that cellular traction forces modulate cellular senescence by promoting chromatin accessibility, particularly at regions associated with FOXO1 expression. This localized chromatin remodeling facilitates FOXO1 activation, which serves as a critical mediator linking cell mechanics to transcriptional and functional changes that regulate senescence. These findings highlight the role of mechanical forces in orchestrating chromatin dynamics and underscore FOXO1 as a key target in the mechanotransduction-mediated regulation of aging.

overall_design: Bone marrow aspirates were obtained from patients aged 60–80 years (old group) and 18–30 years (young group). Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured by plating 1 mL of bone marrow into T-75 flasks containing growth medium supplemented with 10% fetal bovine serum (Gibco). BMSCs at passages 1–2 was used for all downstream experiments. To enhance cellular traction forces, senescent BMSCs were seeded onto a stretching device (Cell&Force, Cell Tank, Hangzhou Surface&Force Technology Co., Ltd) and subjected to cyclic mechanical stimulation at 5% strain and 0.02 Hz for 2 h. Conversely, to attenuate traction forces, young BMSCs were cultured on soft hydrogels with a shear modulus of 1.5 kPa for 24 h.

first: Qiang

last: Wei

first: Xiaojing

last: Liu


title: Clonal CD8+ T Cells Populate the Leptomeninges and Coordinate with Immune Cells in Human Degenerative Brain Diseases

city: New York

first: Ryan

last: Hobson

state: New York

institute: Columbia University

summary: Meningeal immune cells monitor the central nervous system (CNS) and influence neuroinflammation in mice, but the human leptomeningeal immune landscape and the changes that occur in this immunological niche in neurodegeneration remain underexplored. We performed single-cell RNA and T cell receptor (TCR) sequencing of 99,625 high-quality immune cells from 57 leptomeninges and brain samples from donors with Alzheimer’s disease (AD), amyotrophic lateral sclerosis, and Parkinson’s disease and found that while the leptomeninges are home to highly clonally expanded CD8 tissue-resident memory (TRM) T cells, the maximal level of clonal expansion was decreased in AD in comparison to non-neurodegenerative controls. Intra-patient paired tissue analysis further revealed that brain and leptomeningeal TCR repertoires share significant similarities, but tissue-specific clones emerge in AD. Finally in AD, the degree of CD8 TRM clonal expansion was positively correlated with microglial TGFB2, suggesting that brain and leptomeningeal immune cells coordinate their activities in AD. In addition to identifying key inflammatory dynamics in the human degenerating CNS, this study establishes a foundational resource for future studies that could inform treatment for AD and other neuroinflammatory diseases.

overall_design: scRNA/TCR sequencing of CD45+ cells isolated from human postmortem leptomeninges and brain

first: Samuel

last: Levy

first: Delaney

last: Flaherty

first: Harrison

last: Xiao

first: Benjamin

last: Ciener

first: Hasini

last: Reddy

first: Nick

last: Zabinyakov

first: Chitra

last: Singal

first: Christine

middle: Y

last: Kim

first: Andrew

middle: F

last: Teich

first: Neil

last: Shneider

first: Elizabeth

last: Bradshaw

first: Wassim

last: Elyaman


title: DOT1L provides transcriptional memory through PRC1.1 antagonism [ChIP-Seq]

city: Melbourne

first: Daniel

last: Neville

state: Victoria

address: 99 Commercial Road Level 6, Alfred Centre

department: Australian Centre for Blood Diseases

institute: Monash University

summary: DOT1L and Menin are essential cofactors for the oncogenic activity of MLL-fusion proteins (MLL-FPs) in leukaemia. However, the mechanisms underpinning the therapeutic effects of their inhibitors remain unclear. Here, we identify a critical role for the non-canonical Polycomb repressive complex 1.1 (PRC1.1) in mediating the cellular responses to DOT1L and Menin inhibitors. Menin inhibition induces PRC1.1-dependent deposition of H2AK119ub to silence a subset of MLL-FP targets, whereas DOT1L inhibition results in a genome-wide increase in H2AK119ub. We show that enhanced PRC1.1 activity arises specifically from the progressive loss of DOT1L-mediated H3K79 methylation, independent of MLL-FP displacement or transcriptional repression. This regulatory crosstalk is conserved across cell types and is driven by direct biochemical antagonism between H3K79 methylation and PRC1.1 activity. Together, our findings establish DOT1L as a component of transcriptional memory co-opted in leukaemia and suggest it serves as the missing link balancing the opposing forces of the MLL-Polycomb system.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: ChIP sequencing of AML cell lines (murine FLAG-MLLAF9 and MOLM13) and K562 cells with and without DOT1L or Menin inhibitor treatment. ChIP-sequencing of HuDEP-2 (human erythroid progenitors) and murine embryonic stem cells with and without DOT1L inhibitor treatment.

first: Omer

last: Gilan


title: Genomic and transcriptomic analysis of Japanese melanoma reveals candidate biomarkers for immune checkpoint inhibitor responders.

status: Public on Nov 21 2025

city: Tokyo

first: Norio

last: Tanaka

address: Ariake 3-8-31, Koto

institute: Japanese Foundation Cancer Research

summary: Background Immune checkpoint inhibitor (ICI) has greatly improved the prognosis of advanced melanoma. Whereas the efficacy in Japanese patients has been found to be lower than Caucasian, the genomic and transcriptomic features associated with response to ICI of Japanese melanomas remain to be elucidated. Patients and methods Total 129 tumour samples from 78 melanoma patients, who received therapeutic regimens with or without ICI treatment, were collected at 13 institutions in Japan. We performed exome and RNA sequencing and investigated the association of genomic and transcriptomic factors with clinical efficacy of ICI therapy. Time-course data were also analysed. This is the first and largest genomic cohort study for Japanese melanoma, in which tumour samples were prospectively analysed. Results Number of somatic SNVs of Japanese melanomas is lower than that of TCGA Caucasian data due to the biased distribution of WHO subtypes. Driver subtypes of BRAF, NRAS and NF1 was less prevalent but Triple Wildtype predominantly existed in the Japanese cohort. Whereas exome-wide survey revealed no significant association of mutated genes with ICI response, by transcriptomic analysis we identified inflammation-associated genes including several chemokines and cytokines were highly expressed in responders. Follicular helper T cells estimated by immune-cell composition analysis were found significantly enriched in responders (p = 0.0422). Through time-course transcriptome analysis, in addition to several cytotoxic T-cell genes as previously reported, MARCO on tumour-associated macrophages was found induced by ICI treatment in responders (p = 0.0040). The protein expression of these genes was confirmed by immunohistochemical and multiplex immunofluorescent analyses. Some of these genes can be useful biomarkers for prediction of ICI response in the treatment of Japanese melanoma. Conclusions Through prospective genomic and transcriptomic analyses of Japanese melanoma samples, candidate biomarkers for ICI treatment were identified.

overall_design:
mRNA libraries were generated using the TruSeq Stranded mRNA Library Prep Kit (Illumina, San Diego, CA, USA), following the manufacturer’s instructions. Sequencing of captured DNA was conducted with an in-house HiSeq2500 or HiSeq2000 (Illumina) or outsourced to Macrogen Japan Corp (Aomi, Tokyo).  ***Raw data are not available for this series due to patient privacy concerns. Furthermore, the raw data will not be available through controlled-access resources such as dbGaP or EGA. The IRB prohibits public access to the raw data.

***************************************************************
Submitter's institutional review board prohibits public disclosure of raw data due to concerns about patient privacy.
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title: DOT1L provides transcriptional memory through PRC1.1 antagonism [RNA-seq]

overall_design:
3'RNA sequencing of MOLM13, MV4;11, murine MLLAF9, K562, mESC, HuDEP-2 cells with and without DOT1L and/or Menin inhibitor treatment in control or PCGF1, BCOR KO. RNA-seq experiments were conducted in triplicate.

RNA sequencing of AML cell lines with and without DOT1L or Menin inhibitor treatment. RNA-seq experiments were conducted in triplicate.


title: Multi-omics analysis identifies a microbiota–bile acid–TLR signaling axis driving bladder injury in interstitial cystitis

first: Lede

last: Lin

address: No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, P. R. China

institute: West China Hospital of Sichuan University

summary: Hunner-type interstitial cystitis/bladder pain syndrome (HIC) is a complex and clinically challenging chronic disorder characterized by bladder-centered symptoms, including persistent pelvic pain and urinary urgency frequency, with elusive pathogenesis involving poorly defined multi-system interactions and systemic implications. To investigate upstream drivers of urothelial injury, we employed an integrative multi-omics approach, incorporating metagenomic sequencing, targeted metabolomics of urine and serum, and single-cell RNA sequencing. Our analysis identified Enterococcus avium, Megasphaera micronuciformis, and Fusobacterium nucleatum as the significantly enriched species in HIC patients, with bile acid metabolism appearing as a prominently altered pathway. Metabolomic profiling revealed the elevated levels of taurochenodeoxycholic acid (TCDCA) and tauroursodeoxycholic acid, while single-cell transcriptomic data pointed to TLR3 signaling as a key mediator of urothelial injury. Cross-omics correlation proposed a mechanistic axis involving E. avium, TCDCA, and TLR3 activation. Functional validation using fecal microbiota transplantation, E. avium transplantation, and TCDCA administration demonstrated that this axis contributes to the urothelial barrier disruption and inflammatory responses via TLR3. Intervention with a TLR3 inhibitor demonstrated therapeutic potential. These findings shed light on the pathogenesis of HIC, highlighting the potential role of the gut-bladder axis in disease development. This may contribute not only to the discovery of novel biomarkers but also to the development of personalized treatment strategies targeting specific molecular and microbial pathways.

overall_design: Single-cell RNA sequencing was performed from bladders of 10 Hunner-type IC/BPS patients and 7 PSUI controls.

first: Liao

last: Peng

first: Jia-wei

last: Chen

first: Yuan-zhuo

first: Xing-peng

last: Di

first: Le-de

first: Bo-ya

last: Li

first: Chi

last: Zhang

first: Wei

last: Wang

first: Xiao-shuai

last: Gao

first: Yu-cheng

last: Ma

first: Si-hong

last: Shen

first: Hai-rui

first: Xiao-fang

last: Xu

first: Xiao

last: Zeng

first: Hong

first: Qun

last: Sun

first: Tao

last: Jin

first: De-yi

last: Luo