title: Molecular signatures of maladaptive plasticity in the amygdala in a rat model of chronic neuropathic pain

city: Lubbock

first: Julian

middle: David

last: Cardenas

state: TX

address: 3601 4th Street

department: Pharmacology and Neurosciences

institute: Texas Tech University Health Science Center

summary: Chronic pain, a complex multidimensional disorder, remains a major health care issue and a therapeutic challenge. Neuropathic pain is a chronic pain condition that results from damage or dysfunction in the nervous system. While mechanisms of neuropathic pain at the peripheral and spinal cord level have been extensively studied, pain mechanisms in the brain remain underexplored. The amygdala, a limbic brain region, has emerged as a critical brain area for the emotional-affective dimension of pain and pain modulation. Amygdala neuroplasticity has been associated with pain states, but exact molecular and cellular mechanisms underlying these states and the transition from acute to chronic pain are not well understood.We used an integrative approach that focuses on functional significance and cell type specificity of differentially expressed genes (DEGs) to nominate mechanistic targets for central regulation of chronic pain. Our integrative transcriptomic and bioinformatic analyses identified individual genes (e.g., Cxcl10, Cxcl12, Mbp, Plp1, Mag, Mog, Slc17a6, Gad1, Sst), molecular pathways (e.g., cytokine-mediated signaling pathway), biological processes (e.g., myelination, synaptic transmission), and specific cell types (e.g., oligodendrocytes, glutamatergic and GABA-ergic neurons) affected by chronic pain. Our results also provide evidence for the emerging concept of hemispheric lateralization of pain processing in the amygdala. Overall, our study proposes oligodendrocyte dysfunction in the amygdala, neuroimmune signaling in CeA, and glutamatergic neurotransmission in BLA as mechanistic determinants of and potential therapeutic targets for the management of chronic neuropathic pain.

overall_design: The well-established SNL rat model of neuropathic pain was utilized to induce a stable and long-lasting peripheral neuropathy. Rats were anesthetized with isoflurane (2-3%; precision vaporizer, Harvard Apparatus, Holliston, MA) and underwent surgery to expose and tightly ligate the left L5 spinal nerve using 6-0 sterile silk. A sham-operated control group underwent a similar surgical procedure where the L5 spinal nerve was exposed but not ligated. Topical antibiotic (Bacitracin) was applied daily for 5 days after all surgical procedures to prevent infection.

first: P

last: Presto

first: J

first: G

last: Ji

first: C

last: Bustamante

first: B

last: Kisby

first: O

last: Ponomareva

first: V

last: Neugebauer

first: I

last: Ponomarev


title: The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers [washout RNA-seq]

status: Public on Apr 10 2026

city: Suzhou

first: Peng

last: Xu

state: Jiangsu

address: Office3625 Building703, RENAI ROAD No.199, INDUSTRIAL PARK DISTRICT

department: Suzhou Medical College

country: China

institute: Soochow University

type: Expression profiling by high throughput sequencing

summary: Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.

overall_design: Using the KMT2D dual degradation cell model constructed by oneself, adding drugs for 24 hours, removing drugs for 6 and 24 hours, and collecting cells to extract RNA for sequencing.


title: Variants in PATL1 can cause intellectual disability in humans revealed by modeling in Drosophila and C. Elegans

city: Ankara

first: Efe

last: Dalli

address: Dogol Street

country: Turkey

institute: Ankara University

summary: P-bodies are dynamic, membrane-less organelles that function in mRNA metabolism that are involved in mRNA decay, storage, and translational repression. Here we introduce a new variant of the P-body protein encoding gene; PATL1, identified in an ID patient.

overall_design: Fibroblast cells were obtained from the patient with PATL1 gene mutation. These cells were compared with a control sample.RNASeq is performed to compare two groups.


title: GmJAG1 regulates leaf shape development in soybean through transcriptional control of developmental and hormone signaling genes

city: Urbana

first: Bishal

last: Tamang

state: IL

address: 1201 W Gregory Dr

country: USA

institute: University of Illinois

summary: RNA-seq time-course analysis of soybean (Glycine max) shoot apical meristem (SAM) development comparing broad-leaf (functional GmJAG1) and narrow-leaf (D9H mutation) genotypes. Four genotypes were examined: PI 532462A and LD11-2170 (broad-leaf, functional GmJAG1) and PI 612713B and LD11-7311 (narrow-leaf, D9H mutation in GmJAG1). Samples were collected at five developmental timepoints (TP0-TP4) representing progressive stages of SAM development from vegetative meristem to early leaf emergence. Three biological replicates per genotype-timepoint combination yielded 60 total samples. This study identifies GmJAG1-regulated genes controlling leaf morphology in soybean.

overall_design: Factorial experimental design: 4 genotypes x 5 timepoints x 3 biological replicates = 60 samples. Two broad-leaf genotypes (PI 532462A, LD11-2170) with functional GmJAG1 and two narrow-leaf genotypes (PI 612713B, LD11-7311) with D9H mutation in GmJAG1. Timepoints span SAM development: TP0 (shoo apex), TP1-TP3 (progressive development), TP4 (mature leaf).

first: Tamang

last: Bishal

first: Ainsworth

last: Elizabeth


title: Tet governs transcriptional programs required for intestinal stem cell development and homeostasis

city: Houston

first: Hongjie

last: Li

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: For two decades, Drosophila intestinal stem cells (ISCs) have served as a premier model for studying somatic stem cell biology. Yet, the intrinsic mechanisms driving divergent developmental trajectories of seemingly homogeneous progenitors, directing some to establish adult ISCs and others to differentiate, remain unclear. Here, we identify Tet as an essential transcriptional regulator of ISC establishment. Developmental Tet depletion causes region-specific ISC loss and compromises adult lifespan, while adult-specific loss drives progressive stem cell exhaustion. Overexpression of Tet leads to ISC expansion in both developing and adult guts. Utilizing a comprehensive single-nucleus transcriptomic atlas spanning gut development, we demonstrate that Tet stabilizes progenitor identity by maintaining epithelial integrity, signaling competence, and fate maintenance. By defining this developmental trajectory, we reveal Tet as a critical factor that drives proper ISC maturation and maintains long-term adult epithelial homeostasis.

overall_design:
Single-nucleus RNA-sequencing
Midgut samples were collected from females across each stage: wandering third instar larva (L3), white prepupa (P0), 18hr pupa (P18), 48hr pupa (P48), and day 2 adults (D2).
Genotypes: esg-GAL4/Luciferase RNAi, esg-GAL4/dTet RNAi

first: Niccole

last: Auld

first: Ye-Jin

last: Park

first: Yanyan

last: Qi


title: Intratumoral CD40 agonist sotigalimab in combination with pembrolizumab induces rapid activation of antigen presenting cells and drives anti-tumor responses in non-injected tumors in metastatic melanoma: Results of a phase 1/2 study

city: New Delhi

first: Veena

last: Kochat

state: New Delhi

address: Aruna Asaf Ali Marg

department: Stem Cell Biology Lab

country: India

institute: National Institute of Immunology

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Checkpoint inhibitors (CPIs) benefit metastatic melanoma (MM) patients, but resistance remains a challenge. This phase 1/2 (NCT02706353) study evaluated intratumoral sotigalimab (an anti-CD40 agonistic antibody) with pembrolizumab in 32 CPI-naïve MM patients. Primary endpoints included determining safety and tolerability, the recommended phase 2 dose (RP2D) of sotigalimab, and the objective response rate (ORR). The most common adverse events (AEs) related to sotigalimab were injection-site reactions, pruritus, and fatigue. The ORR was 47% and the disease control rate (DCR) was 91% for all patients, and 50% and 92% at the RP2D, respectively. Multiomic biomarker analyses of tumor and blood samples collected before and during treatment demonstrated that sotigalimab effectively engaged the CD40 pathway, boosting the infiltration and activation of myeloid cells, including CD11c+DC-LAMP+ dendritic cells (DCs) and macrophages. The combination therapy activated both innate and adaptive immunity, in both injected and non-injected tumors. TCR sequencing analysis showed increased T-cell clonality with expanded new clones shared between injected and non-injected tumors. Clinical responses correlated with these immunologic changes, but not with baseline immunological features associated with response to anti-PD1 monotherapy. In the B16 melanoma mouse model, single- cell RNA sequencing analysis showed that the combination therapy enhanced antitumor immunity and reduced the immunosuppressive tumor environment. These findings suggest that intratumoral sotigalimab may enhance anti-PD1 therapy, supporting the need for further randomized phase 2 trials to better evaluate its therapeutic potential in the 'in situ' immunization approach.

overall_design: Single cell multiome was performed in 12 samples of tumor tissue obtained from 3 patients at different time points (BL, C1D3, C1D8 and C2D1) with melanoma after administration of Intratumoral CD40 agonist sotigalimab in combination with pembrolizumab

first: Kochat

last: Veena

first: Arslan

last: Emre

first: Rai

last: Kunal

first: Bentebibel

last: Salah-Eddine

first: Diab

last: Adi


title: Integrated long- and short-read transcriptomics define TRP channel expression in adult mouse cortex

city: Acton

first: Muhammad

last: Bilal

state: ACT

address: 131 Garran Road

department: Eccles Institute of Neuroscience, The John Curtin School of Medical Research

country: Australia

institute: The Australian National University

summary: Transient receptor potential (TRP) ion channels are polymodal cation channels with well-established roles in peripheral sensory systems, whereas their expression landscape in the adult cerebral cortex remains incompletely defined. This study provides integrated Oxford Nanopore direct RNA sequencing and Illumina RNA-seq datasets from adult mouse cortex, together with Illumina RNA-seq of dorsal root ganglia as a peripheral sensory reference. Three independent cortical biological replicates were profiled on both platforms. These datasets enable quantitative analysis of TRP channel gene- and isoform-level expression, cross-platform comparison of transcript abundance, and full-length transcript characterisation using long-read sequencing aligned to the Ensembl GRCm39 release 115 reference genome. Raw sequencing files and processed gene- and transcript-level expression tables are provided as a resource for transcriptomic analysis of adult mouse neural tissues.

overall_design: Illumina RNA-seq and Oxford Nanopore direct RNA sequencing of adult mouse cortex (n=3 biological replicates), with Illumina RNA-seq of dorsal root ganglia (DRG) as a peripheral sensory reference.

first: Bilal

last: Muhammad

first: Krishnan

last: Karthik Subramanian

first: Sethi

last: A. J.

first: Hayashi

last: Rippei

first: Kheradpezhouh

last: Ehsan


title: BAF complexes maintain accessibility at stimulus-responsive chromatin and are required for transcriptional stimulus responses [RNA-seq]

city: Atlanta

first: Alexander

middle: O. D.

last: Gulka

state: Georgia

address: 1510 Clifton Rd NE

institute: Emory University

summary: Gene regulation relies on cis-regulatory sequence elements (cREs), including enhancers, to alter gene expression in response to developmental and environmental cues. BRG1/BRM-Associated Factors (BAF) chromatin remodeling complexes are required to maintain an “accessible” chromatin state at many cREs, which enables binding by transcription factors (TFs) and other regulatory proteins. However, cREs exhibit a broad range of sensitivity to loss of BAF function, and the basis of this variable dependence on BAF remains unclear. To identify the characteristics of cREs that rely on BAF complexes to maintain chromatin accessibility, we generated time- and dosage-resolved maps of chromatin accessibility changes following acute BAF inhibition in the lymphoblastoid cell line GM12878. We then integrated these results with ChIP-seq data on more than one hundred TFs and histone modifications available for this cell line and used machine learning to identify features that predict changes in chromatin accessibility upon BAF inhibition. We found that several TFs were associated with sensitivity to BAF inhibition, including widely expressed Activator Protein 1 (AP-1) factors and lymphoid lineage-defining TFs such as RUNX3 and PU.1. Surprisingly, we also found that cREs bearing the chromatin signature of “primed” enhancers – characterized by H3K4me1 enrichment in the absence of the “active” enhancer mark H3K27ac – were significantly more sensitive to BAF inhibition than typical active enhancers. Nearly all primed enhancers lost chromatin accessibility within 30 minutes of BAF inhibition. Notably, primed enhancers are known to facilitate transcriptional responses to external stimuli. Thus, we reasoned that BAF function may be required for cells to mount transcriptional stimulus responses. To test this theory, we assessed the effect of acute BAF inhibition on responses to two orthogonal stimuli, interferon gamma and dexamethasone. We found that BAF inhibition was sufficient to prevent chromatin and transcriptional responses to these stimuli. cREs which normally gained accessibility in response to stimulation failed to do so with BAF inhibition, and these cREs were linked to genes with suppressed transcriptional induction upon stimulation. Collectively, our results demonstrate a requirement for continuous BAF activity to enable stimulus response and suggest that defective signal responsiveness may be a pathogenic mechanism in disease states caused by loss-of-function mutations in BAF subunits.

overall_design: RNA-seq profiling of : GM12878 cells after treatment with interferon gamma (IFNg), dexamethasone (Dex), lipopolysaccharide, interleukin 2, tumor necrosis factor alpha, or doxorubicin for 6h; GM12878 cells treated for 1h or 6h with IFNg or Dex, with our without pretreatment for 0.5h with BRM014 (10uM).

middle: O

first: Kihoon

middle: A

last: Kang

first: Ziben

last: Zhou

first: David

middle: U

last: Gorkin


title: The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers [GATA1 RNA-Seq]

first: Peng

last: Xu

overall_design: Using a self constructed GATA1 and KMT2D dual degradation cell model, after adding drugs for 24 hours, cells were collected and RNA was extracted for sequencing.


title: Spatial Transcriptomic Analysis of a Human Bone Marrow Clot Biopsy Using Xenium 5K

city: Chicago

last: Ji

state: Illinois

address: Ward Building Room 3-230/45, 303 E Chicago Avenue

department: Pathology

institute: Northwestern University

summary: A normal human bone marrow clot biopsy was analyzed using the Xenium 5K panel and annotated with BinarySPA.

overall_design: An FFPE bone marrow clot biopsy was used for Xenium analysis. A 5 µm tissue section was analyzed.

first: Honghao

last: Bi

first: Wenjie

last: Cai

first: Pan

last: Wang

first: Kehan

last: Ren

first: Inci

last: Aydemir

first: Ermin

last: Li

first: Johanna

last: Melo-Cardenas

first: Matthew

middle: J

last: Schipma

first: Ching Man

last: Wai


title: Mast cell specific receptor Mrgprb2/X2 regulates bladder immunity during urinary tract infections

city: Richardson

first: Xintong

last: Dong

address: 800 W Campbell Rd

department: Biological Sciences

institute: University of Texas at Dallas

summary: Urinary tract infections (UTIs) are the most common bacterial infections in women. During UTI, the host mounts a rapid immune response to clear the invading pathogen from the bladder. Mast cells are tissue resident immune cells that are found in the bladder lamina propria and can serve as first responders to bacterial infections. Here, we investigated the role of the mouse mast cell receptor Mrgprb2 and its human homologue MRGPRX2 in UTI. During acute UTI, Mrgprb2 is activated by the antimicrobial peptide cathelicidin and mediates mast cell degranulation. Using Mrgprb2 knockout mice, we demonstrated that Mrgprb2 promotes immune cell recruitment and amplifies inflammation, leading to epithelial damage and increased bacterial burden. Pharmacological inhibition of Mrgprb2 with its antagonist osthole improved infection outcomes. Using a humanized MRGPRX2 knock-in mouse in which Mrgprb2 is replaced by human MRGPRX2, we show conserved function of the mouse and human receptors in the bladder. Our findings identify human mast cell receptor MRGPRX2 as a potential therapeutic target to improve patient outcomes during UTI.

overall_design: RNA-seq profiling of 20 total bladders obatined from female WT (C57BL6/J) and Mrgprb2 Knockout (KO) mice aged 7-10 weeks that were transuretherually inoculated with PBS or UPEC strain UTI89 for 24 hours with 5 biological replicates of each.

first: Waris Muhammad

last: Khuwaja

first: Priyanka

last: Pundir

first: Dustin

last: Green


title: TRIM5 integrates hypoglycemic stress and influenza infection

city: Guangzhou

first: Xiting

last: Lv

state: Guangdong

address: No. 232 East Ring Road, Guangzhou Higher Education Mega Center

institute: Guangzhou University of Chinese Medicine

summary: The role of glucose restriction in host antiviral defense remains elusive. Here, we investigate the impact of pre-existing hypoglycemia on host susceptibility to influenza infections. We find that male mouse models with intermittent hypoglycemia exhibit heightened vulnerability to influenza A virus (IAV) infections at low to moderate exposure levels. This vulnerability is attributed to reduced expression of TRIM5 in the lung subsequent to hypoglycemic stress. Hypoglycemic stress activates AMPK protein to down-regulate ERK1/2 signaling and inhibit the transactivation activity of AP-1, thereby suppressing Trim5 transcription. Diminished expression of TRIM5 renders the male animals more susceptible to influenza infections as it compromises pulmonary antiviral immunity by attenuating type I interferon (IFN-I) production and signaling. These findings provide mechanistic insights into how pre-existing hypoglycemia detrimentally impacts host antiviral defense, and establish TRIM5 as a molecular link connecting metabolic stress to innate antiviral immunity.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: For in vivo transcriptomic analysis, lung tissues were collected for RNA sequencing from two mouse cohorts: (1) an intermittent hypoglycemia model (induced by 2 U/kg insulin for 5 consecutive days) and matched controls; (2) the aforementioned hypoglycemic and control mice after a 3-day influenza A virus (IVA) infection. For in vitro analysis, MLE-12 and A549 cells were cultured under normal-glucose (25 mM or 11.1 mM) or low-glucose (1 mM or 1.1 mM) conditions for transcriptomic profiling.

first: Meng

last: Jin

first: Zicing

last: Wu

first: Dihao

last: Xie

first: Hui

last: Chen

first: Wei

first: Jiatian

last: He

first: Yushan

first: Yifei

last: Xiao

first: Xinyu

last: Zhang

first: Junqiao

first: Lianxia

last: Guo

first: Binbin

last: Wei

first: Min

first: Baojian


title: Single cell RNA sequencing of Thrombopoietin deficient cells

city: Tokyo

first: Ayako

last: Nakamura-Ishizu

address: 8-1 Kawadacho Setagayaku

country: Japan

institute: Tokyo Womens Medical University

summary: Single cell RNA sequencing of hematopoietic stem and progenitor cells comparing Thrombopoietin deficient and control conditions in adult and developmental stages.

overall_design: hematopoietic stem and progenitor cell (LSK fraction) was sorted by flow cytometry from Thrombopoietin (Thpo) deficient mice during embryonic and adult stages. For the embryo, LSK cells were sorted from fetal liver cells at E14.5. For the adult, LSK cells were sorted from bone marrows of 8week old mice.

first: Terumasa

last: Umemoto


title: Characterize the effects of L. asaccharolyticus on autistic-like symptoms

city: hong kong

first: Yuqi

state: hong kong (SAR)

address: the chinese university of hong kong

country: Hong Kong

institute: the chinese university of hong kong

summary: Accumulating evidence has revealed a strong link between the gut microbial community and ASD symptoms mediated by the gut–brain axis; however, ASD-specific microbial markers and the underlying mechanisms for targeted interventions remain unclear. Based on our previous identification of Lawsonibacter asaccharolyticus loss as a candidate ASD marker, we performed bacterial intervention in the BTBR ASD mouse model (C57 mice as healthy controls). Bulk RNA-seq was conducted on brain cortex and colon sections. In vitro validation: SH-SY5Y neuronal cells were treated for 24 h with bacterial filtrate, its derivative metabolite oleoylethanolamide (OEA), or butyrate (BA); untreated cells served as controls. All samples were subsequently analyzed by bulk RNA-seq.

overall_design: In vivo study, we performed bacterial intervention in the BTBR ASD mouse model, with C57 mice serving as healthy controls. Mice were divided into three groups: C57 control mice (c57), BTBR mice receiving vehicle (G1), and BTBR mice receiving L. asaccharolyticus intervention (G3). Brain cortex (c57=3, G1=3, G3=6) and colon sections (c57=5, G1-=9, G3=10) were collected from all animals for bulk RNA-seq analysis. In vitro study, SH-SY5Y neuronal cells were cultured and subjected to four treatment conditions for 24 h: untreated control (NC=6), bacterial filtrate (LAW=3), the bacterial derivative metabolite OEA (OEA=3), and butyrate (BA=3). Following treatment, cells were harvested for bulk RNA-seq


title: Spatial transcriptomics analysis of dual-positive spots

city: Bronx

first: Jeffrey

middle: E

last: Pessin

state: NY

address: 1301 Morris Park Avenue

department: Medicine and Molecular Pharmacology

institute: Albert Einstein College of Medicine

summary: It is generally accepted that hepatic gluconeogenesis is active in the fasted state and inactive in the fed state. In contrast, de novo lipogenesis is active in the fed state and is inactive in the fasted state. We report a subset of periportal spots (hepatocytes) in spatial transcriptomics that are positive of both Pck1 and Fasn.

overall_design: We performed spatial transcriptomics on a) normal chow diet fed C57Bl/6J mouse, b) 3-month high-fat diet fed C57Bl/6J mouse, and c) humanized liver mouse.

first: Junichi

last: Okada

first: Li

last: Liu

first: Kosaku

last: Shinoda

first: Takeshi

last: Saito


title: Reducing CETP activity prevents memory decline in an Alzheimer’s disease mouse model.

city: Montreal

first: Lisa

middle: M

last: Munter

state: QC

address: 3649 Sir-William-Osler Promenade

department: Pharmacology and Therapeutics

country: Canada

institute: McGill University

summary: Epidemiological studies have shown that lower activity of the cholesteryl ester transfer protein (CETP) correlates with reduced Alzheimer’s disease (AD) risk. While small molecule CETP inhibitors like evacetrapib have previously been assessed for cardiovascular diseases, their involvement in AD has not been investigated. Here, we establish CETP as a novel pharmacological target for AD treatment. Using CETP transgenic mice crossed to a mouse model of amyloidosis and administering evacetrapib, we provide evidence that CETP inhibition maintained memory independent of classic AD markers, increased hippocampal cholesterol, altered plasma lipoproteins, and changed transcription of genes linked to brain barriers. Using proteomic data of cerebrospinal fluid (CSF) from cognitively unimpaired at-risk individuals at risk for AD in the PResymptomatic EValuation of Experimental or Novel Treatments for AD (PREVENT-AD) cohort, we confirm that our mouse model reflects physiological changes in pre-symptomatic human subjects. We propose the repurposing of CETP inhibitors as an effective therapeutic strategy to delay or prevent cognitive impairment in AD.

overall_design: RNAseq of bulk RNA from mouse brains; genotype CETP transgenic or APP/CETP transgenix; treatment vehicle or evacetrapib

first: Jasmine

last: Phénix

first: Isabel

last: Sarty

first: Megan S.

last: Katz

first: Hannah

last: Nie

first: Anja

last: Kerksiek

first: Robert S.

last: Kiss

first: Dieter

last: Lütjohann

first: William A.

last: Pastor

first: Judes

last: Poirier

first: Lisa Marie


title: Role of non-coding RNAs in classical hodgkin’s lymphoma treated within the EuroNet-PHL-C2 study

city: Giessen

first: Vijay

middle: Kumar

last: Singh

address: Feulgenstrasse 12

department: Department of Pediatric Oncology, Hematology, and Immunodeficiencies

country: Germany

type: Non-coding RNA profiling by high throughput sequencing

summary: Pediatric Hodgkin lymphoma (HL) is a highly curable malignancy, yet a significant proportion of patients show inadequate early treatment responses despite intensive chemotherapy. The ability to identify these patients at diagnosis or early during therapy is critical for guiding treatment intensity and improving long‑term outcomes while minimizing unnecessary toxicity. MicroRNAs (miRNAs) have emerged as promising biomarkers in HL due to their stability in blood, ease of detection, and central role in regulating gene expression relevant to tumor biology. This study aims to determine whether specific microRNA (miRNA) expression patterns can serve as predictive and prognostic biomarkers in pediatric Hodgkin lymphoma. It will identify signatures—defined by upregulated oncogenic and/or downregulated tumor‑suppressive miRNAs—associated with inadequate early PET (ERAqPET) responses after two cycles of OEPA chemotherapy. miRNA profiles at diagnosis and during treatment will be compared between ERAqPET‑positive and ERAqPET‑negative patients, and correlated with treatment outcomes to establish a biomarker profile for early risk stratification. The goal is to develop a clinically applicable tool to identify high‑risk patients before or early in therapy, enabling tailored treatment that preserves high cure rates while minimizing long‑term adverse effects.

overall_design: Small RNA sequencing was performed on serum samples from 35 pediatric patients with classical Hodgkin lymphoma, treated under the EuroNet‑PHL‑C2 trial, collected both before the start of therapy and after induction therapy.

first: Marius

last: Rohde

last: Körholz


title: The role and inheritance of gene body methylation in an invertebrate

city: London

first: Alex

last: de Mendoza

address: Mile End Road. Fogg Building 5.14

department: School of Biological and Behavioural Sciences

country: United Kingdom

institute: Queen Mary University of London

summary: DNA methylation is traditionally associated with silencing, yet in invertebrates most methylation accumulates in actively transcribed gene bodies, posing a longstanding paradox. Gene body methylation (gbM) has been hypothesized to stabilize gene expression, suppress intragenic transcription, or mediate environmental responses, yet direct experimental evidence for its function remains limited. Here, we use the cnidarian Nematostella vectensis to demonstrate that loss of DNA methylation results in viable embryos with only mild effects on gene expression. Instead, methylation depletion leads to extensive aberrant accessibility and spurious transcriptional initiation, particularly associated to transposable elements within normally methylated gene bodies. This supports a model in which gbM suppresses cryptic regulatory activity in broadly transcribed regions. We further show that abnormal methylation patterns are partially restored in the germline, with recovery biased toward transcriptionally active regions and excluded from repressive chromatin. These epimutations are inherited into the next generation, revealing the absence of epigenetic reprogramming. Our findings uncover a conserved protective role for gbM, demonstrate its capacity for transgenerational inheritance, and highlight its potential as a regulatory substrate for natural selection.

overall_design: Nematostella embryos were treated with GSK-3484862 for 25 hours post fertilization, or DMSO as control. Those embryos were then collected for RNA-seq, ATAC-seq, and EM-seq, to determine the transcriptional and epigenomic responses to DNA methylation loss. Adults resulting from those same treated individuals were crossed in a F1 generation. Those were also grown to 25 hpf, where EM-seq, ATAC-seq and RNA-seq were collected, to compare with the transcriptome and epigenome of the previous generation. We also generated crosses between wild type and GSK-treated individuals that were sequenced with Oxford Nanopore, to assess methylation inheritance at the haplotype level.

first: Lan

last: Xu

first: Richard

last: Heery

first: Damir

last: Baranasic

first: Bojan

last: Žunar

first: Boris

last: Lenhard


title: The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers [CUT&RUN]

first: Peng

summary: By using an unbiased genetic screen and proteome profiling in human erythroblast, we identified and verified KMT2D as an essential factor for human erythropoiesis.  Accordingly, we observed that KMT2D is indispensable for the activation of erythroid signature genes in a stage dependent manner. Moreover, to further study the direct transcriptional regulatory role of KMT2D, we established two endogenous N-terminus AID-KMT2D system in t human erythroblast cell lines and systematically investigated the effects of acute KMT2D loss by auxin-inducible degron system on transcriptional programs and chromatin accessibility. By integrating multi-omics datasets, we revealed that acute KMT2D loss notably suppressed the subset of GATA1 downstream targets. Importantly, we profiled the specific genome-wide occupancy of KMT2D by comparison between the presence and absence of KMT2D in AID model.  Strikingly, KMT2D occupies over hundreds of erythroid specific genes mostly on their promoters. More importantly, we revealed that the KMT2D co-localized with GATA1 in numerous erythroid genes and the occupancy of GATA1 significantly reduced after KMT2D degradation. These results suggest KMT2D is indispensable for the enhancer-binding of GATA1 in gene expression in erythroid lineage specification.

overall_design: The CD34+ HSPC derived erythroblasts used in the experimen. We conducted CUT&RUN experiments using KMT2D antibodies.


title: Multiomic profiling reveals the regulation of important im-mune genes by PU.1 in porcine alveolar macrophages.

city: Yangzhou

first: Juan

last: Yang

address: 大学南路88号

department: College of Veterinary Medicine

institute: Yangzhou University

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

overall_design: Refer to individual Series


title: Evaluation of epithelial growth from colon organoids in Transwell systems and the impact of growth factors

city: South San Francisco

first: Xinming

last: Tong

state: California

address: 1 DNA Way

institute: Genentech Inv.

summary: To investigate the epithelial development of colon organoids cultured on Transwell plates, gene expression analysis was conducted at various stages of differentiation. The effects of multiple growth factors, including epidermal growth factor (EGF), transforming growth factor-alpha (TGFα), keratinocyte growth factor (KGF, also known as FGF10), and trefoil factor 3 (TFF3), as well as cytokines such as interleukin-2 (IL-2) and interleukin-10 (IL-10), on epithelial development were also evaluated.

overall_design: Colon organoids were dissociated and plated onto Transwell inserts in growth medium for 2 days, followed by a switch to differentiation medium for 7 days. RNA expression was measured at day 1 and day 2 in the growth medium, as well as at days 1, 3, 5, and 7 in the differentiation medium. To examine the effects of growth factors, all factors were added to the differentiation medium at a consistent concentration of 2.5 nM, and RNA expression was analyzed on day 9.

first: Tong

last: Xinming

first: Li

last: Jing


title: Deciphering hypoxia related glioblastoma-associated macrophages and predicting prognostic markers by single-cell, spatially-resolved transcriptomics and experimental analysis

city: Wuhan

first: fangyu

last: wang

state: Hubei

address: Donghu Road, No. 115, Wuchang District

institute: Wuhan university

summary: Glioblastomas (GBM), the most common and lethal type of primary brain tumor in adult, currently lack effective treatment and prognostic indicators. Hypoxia, a pathology promoting tumor progression in most solid tumors, has been reported to exhibit a negative correlation with GBM prognosis. Hypoxia related tumor-associated macrophages (hTAMs), the major cellular component of hypoxic regions, have not being systematically studied. We characterized the transcriptomic identity of hTAMs at the single-cell level, simultaneously discovering signatures indicative of poor outcomes. Immunofluorescent staining and spatially resolved transcriptomics revealed pronounced disparities regarding the morphology and distribution of TAMs between hypoxic and non-hypoxic regions of GBMs. We identified ARL4C and HSPA5 as prognostic indicators, exhibiting spatial patterns congruent with hypoxic regions and predicting worse outcomes, verified by qPCR and cell culture. Intercellular communication analysis using single-cell-omics revealed that hypoxia related GBM tumor cells (hGBM cells) exploit the TIMP1/LRP1 ligand-receptor axis to modulate hTAMs, resulting in a worse prognosis. Our study has offered clinically prognostic indicators, along with potentially therapeutic targets for GBMs.

overall_design: The glioma specimens, identified as IDH wild-type grade IV based on postoperative pathology after intraoperative resection, were collected. Subsequently, RNA extraction and concurrent sequencing were performed directly on the obtained tissues.

first: Jingcao

last: Chen

first: Fangyu

last: Wang

first: Haoyu

first: Yigang


title: Identification of a novel subset of hepatocytes that are simultaneously gluconeogenic and de novo lipogenic in the fed state and are naturally insulin resistant

first: Jeffrey

last: Pessin

summary: It is generally accepted that hepatic gluconeogenesis, the synthesis of glucose from other carbon substrates (i.e.: glycerol, pyruvate, amino acids), is active in the fasted state and inactive in the fed state. In contrast, de novo lipogenesis (synthesis of fatty acids) is active in the fed state and is inactive in the fasted state. However, RNAPII ChIP-seq demonstrated that periportal but not pericentral hepatocytes display a basal (fed state) transcriptional activation of gluconeogenic genes that correlated with the basal level of gluconeogenic mRNA expression. Targeted single cell RNA-seq, HCR RNA-FISH, and PrimeFlow identified a subpopulation of periportal hepatocytes (approximately 10% of total hepatocytes) that simultaneously co-express both gluconeogenic and lipogenic genes in the fed state. These dual-positive hepatocytes identified in normal mouse livers are also present in human hepatocytes from humanized mouse livers. Spatial metabolic imaging coupled with stable isotope tracing analyses at the single cell level demonstrated that these individual hepatocytes simultaneously undergo both gluconeogenesis and de novo lipogenesis. Euglycemic-hyperinsulinemic clamps coupled with PrimeFlow analyses further demonstrated that this novel hepatocyte subpopulation is naturally insulin resistant. Moreover, high-fat diet-induced insulin resistance and hepatic steatosis were accompanied by an increase in the number of these dual-positive hepatocytes, suggesting a paradigm shift in our understanding of how the liver becomes insulin resistant. Taken together, these data demonstrate the existence of a unique, naturally insulin-resistant subset of mouse and human periportal hepatocytes that have the capacity to simultaneously undergo both gluconeogenesis and de novo lipogenesis.

overall_design:
ChIP-seq of RNAPII subunit B1 (Rpb1) in isolated total primary hepatocytes from wild type C57BL/6J mouse liver in fed and fast 24h conditions.
ChIP-seq of RNAPII subunit B1 (Rpb1) in isolated periportal (PP) and pericentral (PC) hepatocytes from wild type C57BL/6J mouse liver in fed and fast 16h conditions.

first: Austin

last: Landgraf

last: Liu

first: Junichi

last: Okada

first: Kosaku

last: Shinoda


title: Peripheral serotonin regulates epidermal differentiation and dermal homeostasis

city: Paris

first: Benedicte

last: Oules

address: 123 bvd Port Royal

country: France

institute: INSERM Université Paris Cité

summary: Serotonin is a neurotransmitter with key peripheral functions including regulation of vascular tone, immune responses and tissue repair. It has been shown that it is expressed in skin but its role in skin homeostasis remains unclear. We conducted transcriptomic analyses to elucidate the effects of serotonin deficiency on epidermal and dermal compartments using tryptophan hydroxylase 1 knockout mice. Our results revealed that peripheral 5-HT plays a role in epidermal differentiation, barrier integrity and homeostasis of the dermal compartment.

overall_design: RNA-seq profiling of dorsal skin samples from 3-months wild type mice and their TPH1 knock-out derivates

first: Matar

last: Stéphanie

first: Petit

last: Anne-Cécile

first: Mansour

last: Nathalie

first: Flipo

last: Justine

first: Gendrot

last: Benoit

first: Kanaan

last: Peter

first: Fouquet

last: Guillemette

first: Gaillard

last: Raphaël

first: Aractingi

last: Selim

first: Oules

last: Bénédicte


title: TRAPPC4 resists ferroptosis and promotes head and neck squamous cell carcinoma progression by regulating GPX4 protein stability via TRIM55 [CUT&Tag]

city: hefei

first: Wentao

last: Zhang

state: anhui

address: meishan road

institute: anhui medical university

summary: Ferroptosis resistance continues to be a major challenge in the treatment of head and neck squamous cell carcinoma (HNSCC), yet the molecular mechanisms driving this resistance remain inadequately understood. Here, we conducted an unbiased genome-wide CRISPR-Cas9 knockout library screen and identified TRAPPC4 as a key protein that resists ferroptosis in HNSCC. Moreover, we conducted experiments using HNSCC cell lines, patient-derived organoids, cell-derived xenograft, patient-derived xenograft, conditional knockout mouse models, and popliteal lymph node and lung metastasis models, which confirmed that TRAPPC4 promotes HNSCC progression by inhibiting ferroptosis. Mechanistically, TRAPPC4 inhibits chromatin accessibility at the TRIM55 promoter, blocking FOS driven TRIM55 transcription, reducing TRIM55-mediated GPX4 degradation, and promoting ferroptosis resistance. We further identified pitavastatin calcium as a TRAPPC4 inhibitor and found that its combination with RSL3 effectively suppressed HNSCC progression. This work reveals the critical role of TRAPPC4-mediated ferroptosis in promoting HNSCC progression and provides a promising therapeutic target for treating HNSCC.

overall_design: Through in-depth analysis of the ATAC-seq (sgTRAPPC4 vs sgNTC) results, we found that FOS is a potential transcription factor regulating TRIM55 transcription. Knockdown of FOS can significantly inhibit the expression of TRIM55 at the mRNA and protein levels. To further clarify whether FOS can directly bind to the upstream regulatory region of TRIM55, we performed CUT&tag.

first: Zhao

last: Ding

first: Yanxun

last: Han

first: Xiaojun

last: Zha


title: TRAPPC4 resists ferroptosis and promotes head and neck squamous cell carcinoma progression by regulating GPX4 protein stability via TRIM55

overall_design: To elucidate the specific mechanism by which TRAPPC4 confers ferroptosis resistance in HNSCC, we performed RNA-seq on TRAPPC4 knockout (sgTRAPPC4-1) cells and their corresponding control (sgNTC) cells.


title: The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers

city: Suzhou

first: Peng

last: Xu

address: Office3625 Building703, RENAI ROAD No.199, INDUSTRIAL PARK DISTRICT

institute: Soochow University

summary: Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.

overall_design: To examine the genome-wide effects of KMT2D depletion on H3K4me1, we performed Cut&Run for H3K4me1 in AID-KMT2D HUDEP-2 cells before and after 5-Ph-IAA treatment for 24 hours.


title: Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma [HiC]

city: Bethesda

first: Zachary

last: Batz

state: MD

address: 6 Center Dr Bldg 6, Rm 303

department: NEI

institute: NIH

summary: The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes.  By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.

overall_design: Low coverage traditional Hi-C (pre-capture) and promoter-contact enriched Hi-C (post-capture) of control and dexamethasone-treated human trabecular meshwork cells

first: Nivedita

last: Singh

first: Jayshree

last: Advani

first: Milton A

last: English

first: Rupalatha

last: Maddala

first: Ponugoti Vasantha

last: Rao

first: Anand

last: Swaroop


title: Pathogen-specific immune responses might underlie divergent outcomes of coronavirus and influenza infection in the natural porcine host

city: Pirbrigh

first: liu

last: yang

address: Ash Rd

institute: The Pirbright Institute

summary: Coronaviruses and influenza A viruses are major respiratory pathogens with pandemic potential. Using pigs as a translational large-animal model, we compared the virulence, pathogenesis, and immune responses to porcine respiratory coronavirus (PRCV) and pandemic H1N1 2009 influenza virus (pH1N1). PRCV infection resulted in prolonged viral shedding, more severe lung pathology, and higher viral loads in lung tissue and bronchoalveolar lavage fluid, accompanied by pronounced epithelial necrosis and inflammation. Single-cell RNA sequencing at 12 days post-infection revealed distinct transcriptional signatures and immune activation patterns. PRCV induced stronger mucosal and systemic immunity, with elevated IFN-γ, TNF, and IL-2-secreting T cells, and greater numbers of antigen-specific B cells in blood and airways. Nasal microbiome profiling identified both shared and virus-specific alterations. Together, these findings highlight fundamental differences in coronavirus and influenza virus–host interactions and establish the pig as a powerful comparative model for studying respiratory virus pathogenesis and immunity.

overall_design: We generated single-cell suspensions from lung tissue of control (n = 4), PRCV-infected (n = 4 at 1 DPI and n = 4 at 12 DPI), and pH1N1-inoculated (n = 3 at 1 DPI and n = 5 at 12 DPI) pigs, a total of 20 samples.

first: Ehsan Sedaghat

last: Rostami

first: Liu

last: Yang

first: Ashutosh

last: Vats

first: Basudev

last: Paudyal

first: Emily

last: Briggs

first: Brigid Veronica

last: Carr

first: Graham

last: Freimanis

first: Ines

last: Ruedas-Torres

first: Tim

last: Downing

first: Christine

last: Rollier

first: Katherine

last: Marougka

first: Cornelis A.M.

last: de Haan

first: Jai

last: Mehat

first: Roberto

last: La Ragione

first: Andrew

last: Muir

first: Arianne C

last: Richard

first: Kristien

last: van Reeth

first: Francisco

last: Salguero

first: Wilhelm

last: Gerner

first: Elma

last: Tchilian


title: Interrogating the mechanistic link between neighborhood deprivation and colorectal cancer risk through gene expression analysis of normal colorectal biopsies

city: Charlottesville

first: Matthew

last: Devall

state: Virginia

address: 1335 Lee Street

institute: University of Virginia

summary: Importance: Neighborhood socioeconomic status has been associated with increased colorectal cancer (CRC) risk, particularly among different racial groups, yet the biological mechanisms underlying this association remain unclear. Objective: To investigate whether neighborhood deprivation, as assessed by Neighborhood Deprivation Index (NDI), is associated with differential gene expression in normal colorectal biopsies; to explore molecular links to CRC risk and to identify potential chemoprevention targets. Design: A cross-sectional study involving transcriptomic analysis of normal colorectal tissues and meta-analysis of gene expression data between African Americans (AA) and European Americans (EA), and an experimental study exposing colon organoids derived from healthy colon biopsies to metformin. Setting: Participants were enrolled in the Cleveland Colon Screening and Risk Factors Study (2012-2018) in metropolitan Cleveland, Ohio. Organoids were derived from colon biopsies of patients undergoing colonoscopy in Charlottesville, Virginia. Participants: Normal colorectal biopsies from AA (n = 34) and EA (n = 23) adults undergoing colonoscopy were analyzed. Colon organoids were derived from AA (n = 4) and EA (n = 6) individuals. RNA-seq data was generated from each participant. Main Outcome(s) and Measures: Differentially expressed genes (DEGs) associated with NDI in normal colorectal biopsies and overlap with DEGs identified in CRC tumor tissues; and association of metformin on NDI-associated, CRC risk gene expression. Results: A total of 237 DEGs were found to be commonly associated with NDI across individual-matched biopsy triplets (right and left colon, and rectum) in both racial groups. Cellular metabolism pathways were amongst the most significantly enriched within identified DEGs. Of the 237 NDI associated DEGs, 82 overlapped with CRC tumor DEGs from a publicly available dataset (TCGA-COADREAD; P=2.21×10⁻⁵; OR=1.83), and nine were prioritized as therapeutic targets, including MYC overexpression (BH=2.48E-12). Metformin exposure in colon organoids also altered the expression of 28 of these genes, with ~79% showing opposite direction, including reduced MYC expression (BH=0.095). Conclusion and Relevance: NDI is associated with CRC-related transcriptional differences. These findings suggest potential molecular mechanisms linking neighborhood deprivation to CRC risk. The observed reversal of gene expression by metformin suggests a potential role for metformin in reducing CRC risk in high NDI-populations, who face greater than average risk of developing CRC.

overall_design: Raw expression count files for each sample were compiled into a single matrix in R (v4.3.2). Gene expression data was filtered to only include genes present on non-sex chromosomes. Further, low expressed genes (genes with an average count per million (CPM) of < 0.5) were excluded from downstream regression analysis, which was carried out in limma. Genes were annotated using the getBM() function of biomaRt. Precision weights and mean-variance of log counts were calculated using the voom method prior to and post the calculation of inter-individual correlations using the dupcor() function in limma, followed by the fitting of a linear model and the computation of moderated t-statistics through the use of an empirical Bayes method (Equation 1): Equation 1. Expression ~ Location + BMI + Sex + Smoking + Age + Batch + NDI BMI: Body Mass Index (log of continuous measure); Sex (Male/Female), smoking (factor; never/former/current); age (scaled and centered continuous measure); and NDI (continuous tertile measure). Batch: RNA extraction date.  Meta-analysis of DEGs was performed using the metaSeq41, package in R. P-values derived from each analysis were used to identify genes that were common across racial groups using the other.one-side.p-values(), while setting weight to equal the size of each analysis. Only genes with common directions of association across analyses that trended towards significance (P<0.10) in each original regression were considered.

first: Li

last: Li


title: Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma

first: Zachary

last: Batz


title: An Antagonistically Pleiotropic Gene Regulates Vertebrate Growth, Maturity and Aging

city: Jerusalem

first: Itamar

last: Harel

address: Givat Ram

department: Genetics

country: Israel

institute: The Hebrew University of Jerusalem

summary: The antagonistic pleiotropy theory of aging predicts genetic trade-offs between early-life and late-life fitness. However, empirical evidence for these trade-offs in vertebrates remains scarce, particularly in the context of ecologically relevant life histories. Here, we identify vestigial-like 3 (vgll3), a transcription cofactor previously linked with age at maturity in humans and Atlantic salmon through GWAS studies, as an antagonistically pleiotropic gene in turquoise killifish (Nothobranchius furzeri). By disrupting two conserved vgll3 isoforms, we show that reduction of vgll3, in an isoform- or dose-dependent manner, accelerated male growth and reproductive development. This indicates that vgll3 regulates male sexual maturity. However, early-life benefits come at a late-life cost, as older mutant males with a disrupted long isoform develop melanoma-like tumors, validated via transplantation into immunodeficient rag2 models, and exhibit increased age-related mortality rate. These findings highlight vgll3 as a key regulator of vertebrate life-history trade-offs, balancing early-life fitness with late-life disease risks.

overall_design: Primary cells-derived from the killifish tails. Each sample varied by genotype (wild-type, homozygous mutation in Exon1, or Exon3). Two technical replicates were used for each sample.

first: Eitan

last: Moses

first: Marva

last: Bergman

first: Tehila

last: Atlan

first: Elizabeth

last: Duxbury

first: Roman

last: Franěk

first: Omer

last: Ben Dor

first: Henrik von

last: Chrzanowski

first: Enas

middle: R

last: Abu-Zhayia

first: Shay

last: Kinreich

first: Nabieh

last: Ayoub

first: Ido

last: Ben-Ami

first: Alexei

last: Maklakov


title: Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma [CUT&Tag]

overall_design: CUT&Tag of control and dexamethasone-treated human trabecular meshwork cells

first: Nivedita

last: Singh

first: Jayshree

last: Advani

first: Milton A

last: English

first: Rupalatha

last: Maddala

first: Ponugoti Vasantha

last: Rao

first: Anand

last: Swaroop


title: The H3K4 methyltransferase KMT2D is an essential cofactor for GATA1 at erythroid gene enhancers [ATAC-seq]

first: Peng

last: Xu

overall_design: KMT2D was knocked out in HUDEP-2 cells, and the resulting chromatin accessibility was profiled by ATAC-seq with Tn5 transposase.


title: isl1a Coordinates Onset and Termination of Regeneration of the Zebrafish Lateral Line

city: Kansas City

first: Shiyuan

middle: (Cynthia)

last: Chen

state: MO

department: Computational Biology

institute: Stowers Institute for Medical Research

summary: Regenerative capacity varies widely across tissues and species. Most regeneration studies have focused on identifying genes and pathways that promote regeneration, whereas mechanisms that inhibit regeneration to enforce organ size control and prevent excessive proliferation remain less well defined. Here, we identify isl1a as a dynamically expressed negative regulator of hair cell regeneration in the zebrafish lateral line. isl1a is highly expressed during homeostasis but becomes transiently downregulated following hair cell loss. Loss of isl1a leads to expansion of support cells and enhanced hair cell differentiation, producing enlarged sensory organs with increased hair cell numbers after injury. Mechanistically, isl1a downregulation increases chromatin accessibility at pro-proliferative loci, including AP-1 transcription factors, and sustains expression of injury- and regeneration-responsive genes. Together, these findings demonstrate that injury-induced downregulation of isl1a promotes the initiation of regeneration, while its subsequent re-expression restricts the duration of the response, thereby fine-tuning hair cell regeneration and maintaining organ size control.

overall_design: RNA-seq profiling of mcherry+ sorted cells from isl1apsi97/she:mcherry sibling and mutant samples at 5dpf in homeostasis and 3 hr post neomycin treatment, and ATAC-seq profiling of mcherry+ sorted cell from isl1apsi97/she:mcherry sibling and mutant samples at 5dpf in homeostasis, 1 hr and 3 hr post neomycin treatment. All conditions were collected in biological triplicates.

first: Paloma

last: Meneses-Giles

first: Tatjana

last: Piotrowski

first: Kaelan J

last: Brennan


title: Small RNA sequencing of adipose tissue derived extracellular vesicles from chow- or HFD-fed male mice

city: Nanjing

first: jin

last: wang

address: No. 321 Zhongshan Road

department: Department of Endocrinology

institute: Drum Tower hospital affiliated to Nanjing university medical school

summary: We identified EVs as novel regulatory factors that mediate adipose tissue–brain communication and are crucial for the central control of whole-body energy homeostasis. Our findings reveal that AT-EVs and their cargo microRNAs (miRNAs) are crucial regulators of central leptin sensitivity. To identify the specific subtypes of miRNAs that responsible for central leptin-sensitizing, we examined the sRNA profiles of EVs extracted from adipose tissue of healthy chow-fed and high-fat diet mice by RNA deep sequencing.

overall_design: Adipose tissue derived EVs were extracted from male mice of the 12-week Chow- or HFD-fed C57BL/6J backgrounds and processed for RNA extraction by Trizol. All sRNA library construction and deep sequencing were performed by Novogene (Tianjin, China).

first: Jin

last: Wang


title: Pre-division TCF1 downregulation determines long-term effector and memory CD8 T cell fates [ATAC-Seq]

city: Nashville

first: Mary

last: Philip

state: TN

address: 777 PRB, 2220 Pierce Ave

department: Medicine

institute: Vanderbilt University Medical Center

summary: ATAC-SEQ analysis of antigen-specific CD8 T cells sorted  from the spleens of Listeria-infected mice at different early timepoints following activation. As a control, we sequenced naive CD8 T cells prior to transfer into infected hosts.

overall_design: CD8+CD90.1+ TAG-specific T cells were sorted from spleens of Listeria-TAG infected mice at 12 hours, 2 days (sorted by cell division and CD25 expression) of antigen exposure, or from spleens of transgenic TCRTAG mice, and ATAC-SEQ was performed.

first: Natalie

last: Favret


title: Pre-division TCF1 downregulation determines long-term effector and memory CD8 T cell fates [RNA-Seq]

summary: RNA-SEQ analysis of antigen-specific CD8 T cells sorted  from the spleens of Listeria-infected mice at different early timepoints following activation. As a control, we sequenced naive CD8 T cells prior to transfer into infected hosts.

overall_design: CD8+CD90.1+ TAG-specific T cells were sorted from spleens of Listeria-TAG infected mice at 12 hours, 2 days (sorted by cell division and CD25 expression), 5 days (sorted on KLRG1 and CD62L expression), and 30 days (sorted on CD44 and CD62L expression) of antigen exposure, or spleens of transgenic TCRTAG mice, and RNA-SEQ was performed.


title: Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis

city: Houston

first: Maria

middle: Elisa

last: Ruiz Echartea

state: Texas

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: We conducted a single cell RNA sequencing experiment to determine the effect of a macropinocytosis inhibitor (5-(N-ethyl-N-isopropyl)-Amiloride, EIPA) in Precision Cut Lung Slices.

overall_design: Precision Cut Lung Slices were inciuhbated with or without EIPA (12.5uM) for 72 hours. Culture media was changed every 36 hours . After treatment, slices were subjected to single cell RNA sequencing trough the 10X Genomics 5' Version 3.1  and sequenced trough the Illumina platform.

first: Konstantin

last: Tsoyi

first: Ivan

last: Rosas

first: Coarfa

last: Cristian

first: Ruiz

last: Maria Elisa

first: Waich

last: Alan


title: Gene-Gene Interactions Between A LMNA Variant and Common Polymorphisms Drive Early-Onset Atrial Fibrillation

city: Chicago

first: Asia

last: Owais

state: IL

address: 840 S Wood Street

department: Cardiology

institute: University of Illinois at Chicago

summary: Atrial fibrillation (AF) is a common arrhythmia with a complex genetic basis, yet the molecular mechanisms linking rare and common variants remain unclear. Using induced pluripotent stem cell-derived atrial cardiomyocytes, we uncover a novel mechanism by which a rare pathogenic LMNA variant encoding Lamin A/C disrupts chromatin accessibility and gene regulation at AF-associated loci. Specifically, reduced accessibility at an SCN5A enhancer harboring an AF-associated variant leads to reduced sodium current, conduction abnormalities, and re-entrant AF. These electrophysiological defects are rescued by CRISPR-mediated activation of the SCN5A promoter and enhancer providing the first molecular evidence of epistatic gene-gene interactions driving arrhythmia risk and mechanistically linking atrial myopathy and AF. At the population level, we demonstrate carriers of LMNA proteinaltering variants with a high polygenic risk score are at two-fold increased risk of earlyonset AF, highlighting the need to integrate rare and common variants for more accurate AF risk assessment.

overall_design: RNA sequencing of WT, LMNA-S143P and S143P corrected iPSC derived atrial cardiomyocytes

first: Hammad

last: Farooq

first: Hanna

first: Prisca

last: Thami

first: Jaime

last: Desantiago

first: Talla

last: Abbas

first: Arif

last: Pavel

first: Bradley

last: Merril

first: James

last: Ware

first: Dawood

last: Darbar


title: Transcriptomic Signatures Confirm Conserved Molecular Responses to Glucocorticoid Receptor Agonists in Fathead Minnow (Pimephales promelas)

city: Duluth

first: Peter

last: Schumann

state: MN

address: 6201 Congdon Blvd

institute: United States Environmental Protection Agency

summary: In this study, fathead minnow larvae were exposed to eight concentrations of two glucocorticoid receptor agonists, dexamethasone and fluticasone, and assessed transcriptome-wide gene expression changes using RNA-seq. Differential gene expression analysis revealed substantial overlap in affected genes between the two compounds, supporting their shared mechanism of action. Transcriptomic points of departure (tPODs) were calculated to identify concentrations at which early transcriptomic responses would likely occur. Functional enrichment analysis identified activated biological pathways and enabled the calculation of biological pathway altering concentrations (BPACs). Both compounds significantly altered pathways related to glucocorticoid activity, with fluticasone showing higher potency in most of the pathways. The significant overlap in differentially expressed genes and enriched pathways provides evidence that transcriptomic profiling can effectively detect shared mechanisms of action between related compounds. These findings support the utility of RNA-seq data in read-across approaches for chemical risk assessment and highlight the conserved molecular responses to glucocorticoid receptor activation in fathead minnows.

overall_design: 5-6 dpf larval fathead minnows were statically exposed to 8 concentrations of dexamethasone and fluticasone (in triplicate) for 24 hourrs. In addition to 3 DMSO negative controls, there was a total of 51 samples. Total RNA was isolated from each larval homogenate and sequenced using an Illumina NovaSeq 6000. Processed RNA-seq data was used to derive gene and signature-based points-of-departures (PODs), measure differentially expressed genes and pathways, and to evaluate relative potency of the chemicals.

first: Cole

last: Alexander

first: Schumann

middle: G

last: Peter

first: Cavallin

last: Jenna

first: Bush

last: Kendra

first: Kasparek

last: Alex

first: Flynn

last: Kevin

first: Villeneuve

middle: L

last: Daniel


title: B12 promotes an inflammatory microenvironment, gut dysbiosis, and potentiates myeloid-biased clonal hematopoiesis

city: Miami

first: Luisa

last: Cimmino

state: Florida

address: 1501 NW 10th Ave, BRB 711

institute: University of Miami

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

overall_design: Refer to individual Series

first: John

middle: P

last: Brabson

middle: D

last: Lyon


title: Orientia tsutsugamushi Ank effectors target lamin A and chromatin to inhibit NF-kB

status: Public on Apr 13 2026

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: Intracellular pathogens inhibit nuclear factor-κB (NF-κB), the key transcriptional regulator of antimicrobial responses, using incompletely defined mechanisms. NF-κB nuclear localization and gene accessibility is mediated by Ser22-phosphorylated lamin A/C (pSer22-lamin A/C). Here, we report that the obligate intracellular bacterium Orientia tsutsugamushi impairs NF-κB nuclear accumulation by targeting lamin A using a cohort of ankyrin repeat (AR)-containing effectors (Anks) that have a PRANC (pox proteins repeats of ankyrin C-terminal) domain. The Anks’ immunomodulatory capability relies on a hydrophilic peptide that binds lamin A and pSer22-lamin A. Positioning of this peptide in an a-helix between the AR and PRANC domains is functionally essential. O. tsutsugamushi and ectopically expressed Ank1, one of the NF-κB-inhibiting Anks, promote pSer22-lamin A localization to the nucleoplasm. Orientia also alters chromatin to a primarily closed state to limit accessibility at many sites including those regulated by lamin A/pSer22-lamin A along with NF-κB and its coactivator, adapter protein 1. Thus, O. tsutsugamushi synergistically modulates lamin A and chromatin accessibility to counteract NF-κB. These findings reveal a strategy by which an intracellular microbe subverts host immunity, reinforces the regulatory link between lamin A and NF-κB, and indicates that pSer22-lamin A activates NF-κB by increasing chromatin accessibility to it and its coactivators.

overall_design: ATAC-seq profiling of uninfected HeLa cells and HeLa cells infected with O. tsutsugamushi at 72 hours post infection.

first: Thomas

last: Siff

first: Paige

last: Allen

first: Haley

last: Adcox

first: Svetlana

last: Blinova

first: Travis

last: Chiarelli

first: Jason

last: Hunt

first: Joseph

last: Wang

first: David

last: Armistead

middle: S

last: Billingsley

first: Nathaniel

last: O'Bier

first: Richard

middle: T

last: Marconi

first: Andrew

middle: K

last: Ottens

last: Carlyon


title: Dehydration promotes intracellular lipid synthesis and lipid accumulation

city: Durham

first: Integrative

last: Bioinformatics

state: NC

address: 111 TW Alexander Drive

department: BCBB

institute: NIEHS

summary: NFAT5 is transcription factor that regulates gene expression in response to hypertonic stress. Here we profile NFAT5 occupancy before and hour following hypertonic stress in mouse inner medulla collecting duct cells, as resource to localize sites with tonicity depend chromatin occupancy.  In addition, we test the occupancy of the active histone mark H3K27ac and the repressive mark H3K27me3.

overall_design: Occupancy of NFAT5 and H3K27 histone marks in mouse IMCD cells under isotonic and hypertonic conditions

last: Watts

first: Juan

last: Arroyo Ornelas

first: Ma

last: Wan

first: Don

last: Delker


title: Acetylated OsWOX13 coordinately regulated drought-responsive and NUE- related genes

city: Wuhan

first: feng

last: zhao

address: No. 1, Shizishan Street, Hongshan District

institute: Huazhong Agricultural University

summary: OsWOX13 is a higher hierarchical regulator of drought resistant and NUE genes

overall_design: To investigate the regulatory mechanism of OsWOX13 acetylation in drought resistance and NUE, we performed RNA-seq using OE13 and OE13-2KR/oswox13-1 plants subjected to drought stress

first: Mingfang

last: Tan


title: Inhibition of the fructose transporter Glut5 boosts androgen production by dysregulating the metabolism of murine Leydig cells

city: Nouzilly

first: Pascal

last: Froment

address: INRAE Nouzilly

department: UMR 7247 INRAE/CNRS/Université de Tours/IFCE

institute: INRAE

summary: Over the past few decades, a significant change in global sugar intake has coincided with a rising incidence of male infertility, which is now a major public health concern. Diets rich in fructose have been implicated in both male infertility and an increased susceptibility to metabolic disorders like obesity, diabetes, and related heart problems. While fructose is known to be present in seminal fluid and crucial for sperm motility, the precise role of fructose in testicular function remains largely unknown. While GLUT5 is recognized as the exclusive fructose transporter for dietary uptake, it is known to be expressed in germ and Leydig cells. Our recent study has shown that disrupting the GLUT5 gene in male mice impairs both spermatogenesis and steroidogenesis. However, its specific role within Leydig cells remained unexplored. We investigated this by inhibiting a murine Leydig cell line (mLTC-1) with MSNBA, a specific inhibitor of GLUT5. To comprehensively understand the molecular mechanisms of GLUT5 in these cells, we employed a multi-omics approach. Exposition to MNSBA reduced intracellular fructose content, limited cell proliferation and enhanced androgen production. The increased production of testosterone was linked to the upregulation of steroidogenesis-related genes such as Hsd3b, and steroidogenic acute regulatory protein (StAR). In Leydig cell, inhibition of GLUT5 modify lipid and carbohydrate metabolism. Lipidomic analysis showed a decrease in cholesterol esters and a shift in the ratio of polyunsaturated fatty acids (PUFAs) to monounsaturated fatty acids (MUFAs). These lipid changes were correlated with alterations in the expression of mRNA encoding enzymes involved in lipogenesis, such as Elovl6. Metabolomics analysis showed a reduction of different metabolite of the glycolysis except for pyruvate and lactate. However, pyruvate molecules could be produced from the higher branched-chain amino acids content. BRB-seq approach has revealed an upregulation of several androgen-sensitive genes such as lactate dehydrogenase A (Ldha) producing lactate and a down regulation of several genes associated to insulin pathway. In summary, Glut5 is involved in Leydig cells for the fructose intake. Perturbation of the Glut5 activity led to an alteration of the energy metabolism but stimulated the androgen production. Because androgens are known to influence spermatogenesis, these findings raise the importance of the fructose intake in the function of male fertility.

overall_design: RNA-seq profiling of mLTC-1 murine Leydig cell line at 0 (control) and 100 µM of N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine, a specific Glut5 transporter inhibiter

first: Aikaterini

last: Kallianioti

first: Guillaume

last: Bourdon

first: Claire

last: Chevaleyre

first: Christine

last: Péchoux

first: Christelle

last: Ramé

first: Jérôme

last: Bourgeais

first: Olivier

last: Hérault

first: Thomas

last: Darde

first: Ingrid

last: Plotton

first: Véronique

last: Douard

first: Joëlle

last: Dupont


title: TRAPPC4 resists ferroptosis and promotes head and neck squamous cell carcinoma progression by regulating GPX4 protein stability via TRIM55 [ATAC-seq]

city: hefei

first: Wentao

last: Zhang

institute: anhui medical university

summary: Ferroptosis resistance continues to be a major challenge in the treatment of head and neck squamous cell carcinoma (HNSCC), yet the molecular mechanisms driving this resistance remain inadequately understood. Here, we conducted an unbiased genome-wide CRISPR-Cas9 knockout library screen and identified TRAPPC4 as a key protein that resists ferroptosis in HNSCC. Moreover, we conducted experiments using HNSCC cell lines, patient-derived organoids, cell-derived xenograft, patient-derived xenograft, conditional knockout mouse models, and popliteal lymph node and lung metastasis models, which confirmed that TRAPPC4 promotes HNSCC progression by inhibiting ferroptosis. Mechanistically, TRAPPC4 inhibits chromatin accessibility at the TRIM55 promoter, blocking FOS driven TRIM55 transcription, reducing TRIM55-mediated GPX4 degradation, and promoting ferroptosis resistance. We further identified pitavastatin calcium as a TRAPPC4 inhibitor and found that its combination with RSL3 effectively suppressed HNSCC progression. This work reveals the critical role of TRAPPC4-mediated ferroptosis in promoting HNSCC progression and provides a promising therapeutic target for treating HNSCC.

overall_design: To elucidate the specific mechanism by which TRAPPC4 confers ferroptosis resistance in HNSCC, we performed Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) on TRAPPC4 knockout cells (sgTRAPPC4) and their corresponding control (sgNTC) cells.

first: Zhao

last: Ding

first: Yanxun

last: Han

first: Xiaojun

last: Zha


title: KMT2D-Mediated H3K4methylation is Essential for GATA1 Transcriptional Activation in Erythropoiesis [ChIP-seq]

city: Suzhou

first: Peng

last: Xu

state: Jiangsu

department: Suzhou Medical College

institute: Soochow University

summary: The regulation of enhancer activity is essential for cell differentiation and different diseases. KMT2D is considered a significant histone methyltransferase that catalyzes H3K4me1 on enhancers and activates the enhancers by recruiting acetyltransferase for H3K27ace. However, how exactly enhancer activation is determined in human erythropoiesis remains incompletely understood. Here, by using an unbiased genetic screen in human erythroblasts, we identified and verified that KMT2D is an essential factor for human erythropoiesis. Accordingly, we observed that KMT2D is indispensable for the activation of erythroid signature genes. Moreover, to further study the direct transcriptional regulatory role of KMT2D, we employed the auxin-inducible degron 2 (AID2) system in human erythroblast cell lines to systematically investigate the effects of acute depletion of KMT2D on transcriptional programs, the genome-wide occupancy of KMT2D and the erythroid master regulator GATA1. Importantly, we revealed that KMT2D colocalized with GATA1 on more than one thousand active enhancers. Moreover, the GATA1 and KMT2D co-localized enhancers exhibit significant higher activities relative to the GATA1 only occupied enhancers. After the depletion of KMT2D, the active histone marks on those enhancers were significantly reduced in accompanying with suppression of the selective targets of GATA1, including numerous erythroid genes (such as ZFPM1, SLC4A1, and EPOR). These results suggest that KMT2D is indispensable for the activation of erythroid gene expression by GATA1. Thus, our results revealed a novel role of KMT2D in the selective dependency of GATA1 on active enhancers, which could impact the transcriptional regulation of KMT2D in both hematopoiesis and blood cancers.

overall_design: We conducted transcriptome and CHIP-SEQ analysis in HUDEP2 cells rapidly degraded and knocked out by KMT2D


title: Gene-Gene Interactions Between A LMNA Variant and Common Polymorphisms Drive Early-Onset Atrial Fibrillation [ATAC-seq]

first: Asia

last: Owais

overall_design: ATAC sequencing of LMNA-S143P and S143Pcorrected iPSC derived atrial cardiomyocytes

first: Hammad

last: Farooq

first: Hanna

last: Chen

first: Prisca

last: Thami

first: Jaime

last: Desantiago

first: Talla

last: Abbas

first: Arif

last: Pavel

first: Bradley

last: Merril

first: James

last: Ware

first: Dawood

last: Darbar


title: The impact of SOGA1 deficiency on gene expression in ovarian cancer cells

city: Hefei

first: Yifan

last: Feng

state: Anhui

address: Jixi Road 218

institute: The Anhui Medical University

summary: SOGA1 is an autophagy-related factor that significantly influences cancer progression.Here, we identified the critical role of SOGA1 in the diagnosis and prognosis of ovarian cancer through bioinformatics analysis.Further functional experiments demonstrated that SOGA1 significantly promotes ovarian cancer progression through GNAI1.RNA-seq analysis revealed that differentially expressed genes downstream of SOGA1 are significantly enriched in the TNF signaling pathway, which was validated by Western blot.In summary, our data provide new molecular insights into ovarian cancer.

overall_design: The SOGA1 SINC and SOGA1 SI OVCA433 ovarian cancer cell lines were used for 3v3 RNA-seq.

first: Min

last: Li


title: Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma [ATAC]

city: Bethesda

first: Zachary

last: Batz

institute: NIH

summary: The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes.  By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.

overall_design: ATAC-seq of control and dexamethasone-treated human trabecular meshwork cells

first: Nivedita

last: Singh

first: Jayshree

last: Advani

first: Milton A

last: English

first: Rupalatha

last: Maddala

first: Ponugoti Vasantha

last: Rao

first: Anand

last: Swaroop


title: Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma [RNA-seq]

overall_design: Total RNA-seq of control and dexamethasone-treated human trabecular meshwork cells


title: TRAPPC4 resists ferroptosis and promotes head and neck squamous cell carcinoma progression by regulating GPX4 protein stability via TRIM55 [CRISPR Screen]

first: Wentao

last: Zhang

address: meishan road

overall_design: Genome-wide CRISPR-Cas9 knockout screening was performed in LIU-LSC-1 cells using the human GeCKOv2A sgRNA library to identify genes involved in ferroptosis resistance. Cells were transduced at an MOI of 0.3 to ensure single sgRNA integration and selected with puromycin (1.5 μg/mL) for 7 days. The resulting mutant pool was divided into two groups and treated with either DMSO (vehicle control) or RSL3 (IC20) for an additional 7 days. After treatment, genomic DNA was extracted from at least 3×10⁷ cells per condition for sgRNA amplification and deep sequencing. Screen results were analyzed using the MAGeCK algorithm to identify enriched or depleted sgRNAs.

first: Zhao

last: Ding

first: Yanxun

last: Han

first: Xiaojun

last: Zha


title: Chromatin topology dynamics of dexamethasone-treated trabecular meshwork identifies 78 causal genes for intraocular pressure and primary open angle glaucoma [CUT&Run]

overall_design: CUT&RUN for histone marks and CTCF performed on control human trabecular meshwork cells


title: G-quadruplexes regulate chromatin accessibility and gene expression in Bloom Syndrome [BlmSynFamily]

city: Tübingen

first: Yingguang Frank

last: Chan

address: Max Planck Ring 9

department: Chan group

institute: Friedrich Miescher Laboratory of the Max Planck Society

summary: Bloom Syndrome (BS) is a recessive genetic disorder characterized by hyper-recombination and genome instability. It is caused by mutations in the conserved RecQ helicase gene, BLM, which is essential in maintaining genome integrity and unwinds various aberrant DNA structures. One such structure is DNA G-quadruplexes (G4s), which have broad regulatory functions. Although putative G4-forming sequences have been previously implicated in BS, it remains unclear what (dys)regulatory role, if any, endogenous G4 structures may play in BS. Here, we profiled chromatin accessibility and gene expression via ATAC-seq and RNA-seq and mapped endogenous G4 via ChIP-seq in wild-type (WT) vs. BS cell lines. We observed that in BS, differential G4 formation positively correlated with both chromatin accessibility and gene expression. Stabilizing G4 in WT cells with pyridostatin partially phenocopied BS. Additionally, data from a BS family showed that regions with increased chromatin accessibility in BS individuals were also enriched for G4-forming sequences. Our data showed that G4 formation is associated with higher chromatin accessibility and gene expression; likely in BS, unresolved G4 increases focal chromatin accessibility, thereby upregulating gene expression. In summary, our results revealed a central role of G4 in the molecular etiology of BS and provide a new perspective on BLM’s regulatory function through G4s.

overall_design: To characterize the chromatin accessbility changes in Bloom Syndrome individuals, we collected ATACseq data from a Bloom Syndrome family and divided the samples into 2 groups: non-patients and patients.Later in the anlaysis, due to low data quality, sample 302 was excluded.

first: Dingwen

last: Su


title: G-quadruplexes regulate chromatin accessibility and gene expression in Bloom Syndrome [RNA-seq]

summary: Bloom Syndrome (BS) is a recessive genetic disorder characterized by hyper-recombination and genome instability. It is caused by mutations in the conserved RecQ helicase gene, BLM, which acts to unwind various aberrant DNA structures. One such structure is DNA G-quadruplexes (G4s), which have broad regulatory functions. Despite previous association between putative G4-forming sequences and BS, it remains unclear what (dys)regulatory role, if any, endogenous G4 structures may play in BS. Here, we profiled chromatin accessibility and gene expression via ATAC-seq and RNA-seq and mapped endogenous G4 via ChIP-seq in wild-type (WT) vs. BS cell lines. We observed that in BS, differential G4 formation positively correlated with both differential chromatin accessibility and gene expression. To test the direct involvement of G4s in the molecular phenotypes in BS, we applied pyridostatin, a G4-stabilizing molecule, in WT cells and showed that G4 stabilization partially phenocopied BS. Additionally, data from a BS family showed that regions with increased chromatin accessibility in BS individuals were also enriched for G4-forming sequences. Our data showed that G4 formation promotes chromatin accessibility and gene expression; likely in BS, unresolved G4 increases focal chromatin accessibility, thereby upregulating gene expression. In summary, our results revealed a central role of G4 in the molecular etiology of BS and provide a new perspective on BLM’s regulatory function through G4s.

overall_design: To characterize the transcriptomic changes caused by BLM-/- , we compared gene expression profiles in BLM-/- and wildtype cells. To characterise the impacts of a small G4 stabilising molecule, PDS on gene expression and if PDS treatment molecularly mimics BLM-/-, we compared gene expression profiles in wildtype cells treated with 0.4%DMSO (as the control) and with 10uM PDS.


title: Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis

first: Scott

middle: Andrew

last: Ochsner

state: TX

department: Molecular and Cellular Biology

summary: We conducted a bulk RNA sequencing experiment to determine the effect of macropinocytosis inhibitor (5-(N-ethyl-N-isopropyl)-Amiloride, EIPA) in lung fibroblasts

overall_design: MRC-5 cells were stimulated with TGF-beta1 (10 ng/ml) for 24 hours in the presence of absence of EIPA (12.5 𝛍M) or DMSO (vehicle).

first: Konstantin

last: Tsoyi

first: Ivan

middle: O

last: Rosas

first: Neil

last: Mckenna


title: SPEN loss drives extra-follicular diffuse large B cell lymphoma with female-specific lethality and TLR pathway therapeutic vulnerabilities

city: New York

first: Matt

last: Teater

state: NY

address: 445 E 69th St

institute: Weill Cornell Medical College

summary: In this study, we explore the interplay between SPEN and NOTCH2 truncating mutations, identifying an alternative, extra-follicular, trajectory of diffuse large B cell lymphomas (DLBCL) transformation. Our findings challenge the traditional germinal centre-centric model of lymphomagenesis, showing that marginal zone B cells (MZB) can give rise to aggressive lymphomas with autoimmune/aged B cells (AiBC)-like features, under the influence of these compound mutations. At a mechanistic level, we found that SPEN loss re-routes NOTCH2-driven transcriptional programs, promoting a ZEB2-driven cell fate that blocks plasmacytic differentiation and skews B cell identity toward a MZB/AiBC mixed phenotype. We further show that SPENTRUNC/NOTCH2TRUNC-mutant lymphomas are associated with reduced overall survival of female DLBCL patients, due to X-chromosomal transcriptional perturbations. By characterizing their unique molecular dependencies, we identify actionable features in this aggressive DLBCL subset, paving the way for new precision medicine strategies that address the disease’s heterogeneity.

overall_design:
RNAseq in murine germinal center B cells, tFL cell line model, PDX samples

scRNA and scATAC-Seq of sorted splenic MZB/FOB/AiBCs of female, unimmunized mice.

SMRT-Seq of CD19+ enriched lymphoma samples from female WT MZB, N2 and SN2 lymphomas

first: Benedikt

last: Pelzer

first: Cem

last: Meydan

first: Ari

last: Melnick


title: Complex Mechanisms of Topoisomerase II Poisons Revealed by Whole-genome Analysis

city: Xiamen

first: Huifen

last: Cao

email: hfcao_bnu@163.com, hfcao@hqu.edu.cn

state: Fujian

address: 668 Jimei Road

department: School of Biomedical Sciences

institute: Huaqiao University

summary: Topoisomerase II (TOP2) represents a vital enzyme which functions by introducing transient DNA breaks to resolve topological issues in DNA and regulate gene expression. The potentially toxic nature of these DNA breaks made the drugs that stabilize them, TOP2 poisons, into highly successful anticancer agents, and research tools. However, despite decades-long widespread usage of these drugs, not much is known about differences in the genome-wide profiles of DNA breaks caused by them. Here, we generated high-resolution genome-wide maps of DNA breaks induced by seven different TOP2 poisons in a human cancer cell line using the SSiNGLe method developed by our group. We found multiple notable differences even between the drugs with highly similar chemical structures, indicating that each poison targets a specific subpopulation of catalytically engaged TOP2 enzymes bound to DNA. The preferential targeting observed may be partly explained by the distinct local sequence preferences we identified for each TOP2 poison. However, our results also indicate that genomic context, chromatin environment, and the heterogeneity of TOP2 cleavage complexes likely contribute. Altogether, this study has potential significant implications for our understanding of the reasons behind the clinical differences among the drugs and the mechanisms of TOP2 function.

overall_design: An in-depth comparison of the genome-wide profiles of DNA breaks caused by different types of TOP2 poisons.

first: Philipp

last: Kapranov


title: Network analysis of normal colon organoids exposed to metformin reveals likely regulatory role for colorectal cancer genome-wide association study candidate genes

city: Charlottesville

first: Matthew

last: Devall

address: 1335 Lee Street

institute: University of Virginia

summary: Here we aimed to define the effects of a three-day, 24-hour repeated dose exposure of metformin (90um) of colon epithelial cell gene expression through RNA-seq and network analysis (WGCNA) of 10 colon organoid lines derived from healthy individuals.

overall_design: Organoid exposure to metformin. Cells were seeded at a density of 1x106 cells per 48 well and exposed daily to media containing metformin  (0.09mmol/L) or vehicle control (water) for three days.At the end of 72 hours, Matrigel was scratched off each well using a pipette tip and placed into sterile Eppendorf tubes. A total of 1mL of complex media was added to each well and then transferred to tubes containing Matrigel, which were then centrifuged at 1200rpm at 4ºC for 5 minutes. The resulting supernatant was carefully removed and 500μL of TrypLE (Gibco #12604039) was added to each pellet, which were placed in the incubator at 37ºC for 10 minutes. Following incubation, TrypLE was neutralized using an equal volume of complex media. Matrigel containing organoids were further disrupted 8-10x using a fine needle before being centrifuged at 1200rpm at 4ºC for 5 minutes. Finally, supernatant was removed and 300µL of RNA Lysis Solution RA1 (with 6µl TCEP) (Clontech/Machery-Nagel RNA XS Kit) was added to each pellet. The contents were then vortexed and stored in a -80oC freezer prior to RNA extraction. RNA-sequencing and library preparation was carried out by a commercial provider.

first: Graham

last: Casey

first: Li

last: Li


title: Extranuclear Epitranscriptomic Mechanisms Control Metastasis

city: Toronto

first: Gobi

last: Thillainadesan

state: Ontario

address: 2075 Bayview Ave., S1-18

department: Biology

institute: Sunnybrook Research Institute

summary: Non-coding RNA and RNA binding proteins play a major role in the nucleus by regulating splicing, transcription, and transcript stability. Here, we show existence of ncRNAs and RNA binding proteins called “R-bodies” within the cytoplasm of metastatic cancer cells.  Biogenesis of R-bodies begins with integrin activation and intracellular accumulation of proteases.  m6A-epigenetically marked MALAT1 was exclusively found in R-bodies and determined to be the core for R-body formation.  Disabling R-bodies using METTL3 inhibitors and RNA therapy against m6A-MALAT1 were effective in halting cell invasion and metastasis dynamics. The extranuclear epitranscriptome unites extracellular and nuclear factors to swiftly induce cancer progression within hours.  This is evidenced by the epigenome generating m6A-MALAT1 in the cytoplasm which goes onto cytoplasmic R-bodies, leading to cancer invasion.  Overall, the epitranscriptome has post-translational activities and is a viable anti-metastasis target.

overall_design: RNA sequencing was done using Novaseq 6000 of RNA immunoprecipitation experiments (RIP). RIP was conducted using MT1-MMP antibody and Rabbit IgG(mock) in MDA-231 cells that were treated with Beta-1-integrin G11 antibody.

first: Olivia

last: Grafinger

last: Thillainadesan*

first: Boyang

first: Yulin

last: Mo

first: Xin

last: Xu

first: Sara

last: Mar

first: Minzhi

last: Sheng

first: Sumaitha

middle: A

last: Islam

first: Jennifer

last: Geddes-McAllister

first: Marc

last: Coppolino

first: Hansen

middle: H

last: He

first: Gang

first: Katarzyna

last: Jerzak

first: Hon

last: Leong


title: Small RNA sequencing of extracellular vesicles extracted from adipose tissue of healthy weight or obese human subjects

city: Nanjing

first: jin

last: wang

address: No. 321 Zhongshan Road

institute: Drum Tower hospital affiliated to Nanjing university medical school

summary: We identified EVs as novel regulatory factors that mediate adipose tissue–brain communication and are crucial for the central control of whole-body energy homeostasis. Our findings reveal that AT-EVs and their cargo microRNAs (miRNAs) are crucial regulators of central leptin sensitivity. To identify the specific subtypes of miRNAs that responsible for central leptin-sensitizing, we examined the sRNA profiles of EVs extracted from adipose tissue of healthy weight and obese subjects by RNA deep sequencing.

overall_design: EVs were extracted from adipose tissues of nondiabetic and diabetic subjects and processed for RNA extraction by Trizol. All sRNA library construction and deep sequencing were performed by Novogene (Tianjin, China).

first: Jin

last: Wang


title: Circulating Transfer RNA Related Fragment (tRF) Abundance After Experimental Endometriosis Induction in Baboons

status: Public on Apr 09 2026

city: New Haven

first: Ramanaiah

last: Mamillapalli

state: CT

address: 310 Cedar Street

department: OBGYN

institute: Yale University

summary: Endometriosis is a chronic systemic disease affecting approximately 10–15% of women of reproductive age, often resulting in chronic pelvic pain and infertility. Despite its high prevalence, diagnosis is frequently delayed. Transfer RNA-derived fragments (tRFs) are an emerging class of small non-coding RNAs that have been implicated in gene regulation and various pathological processes but remain understudied in endometriosis. This study aimed to characterize temporal changes in circulating tRF abundance after experimentally induced endometriosis in a baboon model, with the goal of identifying non-invasive biomarkers for early disease detection. Endometriosis was induced in eight female baboons, and peripheral blood samples were collected at five time points: pre-inoculation and at 3-, 6-, 9-, and 15-months post-inoculation. RNA was extracted from serum samples and sequenced to profile tRF abundance. Differential expression analysis was performed using a linear modeling approach. Significant changes in tRFs were observed as early as three months after induction. Both upregulated and downregulated tRFs were identified at each time point. A ranking based on log fold change and adjusted p-values revealed the ten most significantly altered tRFs, none of which had been previously described in the context of endometriosis. These tRFs demonstrated consistent differential abundance throughout all time points. This is the first study to investigate circulating tRFs in endometriosis. There is a rapid induction of tRFs after the onset of endometriosis in the non-human primate model. Our longitudinal findings suggest that tRFs may serve as promising early biomarkers for endometriosis.

overall_design: Endometriosis was induced in Baboons by inoculating menustrual fluid tissue into peritoneal cavity by laparoscopy surgery, confirmed the lesion development by laparoscopic and histological evaluation. Blood was drawn on at preincoculation, month 3, 6, 9 and 15th and serum was collected and processed for tRFs differential expression (RNA-sequence analysis) across all time-ppoints while proinoculation time point taken as basal expression of these tRFs.

first: Hanna

last: Surmann

first: Niraj

last: Joshi

first: Gregory

last: Burns

first: Asgerally

last: Fazleabas

first: Hugh

last: Taylor