title: A novel CAF population coordinates hyper-suppressive regulatory T cell recruitment and localization in lung cancer [scRNA-seq_PDGFRa+ fibroblasts)

first: Nicholas

last: Arpaia

address: 701 W 168TH ST HHSC 906

institute: Columbia University Irving Medical Center

summary: Across many solid tumor types, cancer-associated fibroblasts (CAFs) are abundant and highly heterogeneous, with distinct subpopulations exerting immunomodulatory functions. Though they have been well characterized in malignancies considered to be highly desmoplastic, how distinct CAF populations in lung adenocarcinoma (LUAD) influence the tumor–immune microenvironment is not well understood. Here, we identify a novel population of immunomodulatory CAFs (imCAFs) in the LUAD tumor microenvironment, characterized by CHL1 expression and enriched in transcriptional programs involving immune regulation and chemokine signaling. Through single-cell and spatial transcriptomics, we demonstrate that imCAFs are spatially colocalized with CXCR3+ regulatory T (Treg) cells, a hyper-suppressive T cell subset that accumulates at the tumor border. Mechanistically, imCAFs produce CXCL9, a key chemoattractant that mediates the recruitment of CXCR3+ Tregs to the tumor, promoting an immunosuppressive microenvironment. Functional profiling reveals that tumor-resident CXCR3+ Tregs possess enhanced proliferative and suppressive capacity and are transcriptionally distinct from CXCR3- counterparts. Genetic ablation of Cxcr3 in Treg cells or Cxcl9 in stromal cells significantly reduces Treg cell accumulation, resulting in enhanced CD8+ T cell activation and decreased tumor burden. Analogous CHL1+ imCAF-like fibroblasts are also observed in human NSCLC samples and were found to colocalize with Treg cells, with increased CHL1 expression in lung tumors being associated with reduced cytotoxicity scores and decreased progression free survival. These findings uncover a critical stromal–immune axis wherein imCAF-derived CXCL9 orchestrates the localization and function of hyper-suppressive CXCR3+ Tregs in LUAD and highlight the imCAF–CXCL9–CXCR3+ Treg cell recruitment circuit as a promising therapeutic target to restore anti-tumor immunity.

overall_design: C57B6/JN mice (n=3) were intravenously injected with 1.5e5 LLC-GFP cells. After 17 days, lungs of mice were harvested. Tumor tissue and normal-adjacent lung tissue were seperated utilizing microdissection techniques and each tissue was labeled using seperate hashtag oligos (HTOs; (n=6)). Usting magnetic bead negative enrichment and single cell sorting techniques, we isolated live GFP-CD45- CD31-, EPCAM-, CD146- PDGFRa+ cells and sequenced using the 10X illumina platform

first: Olivia

last: Ringham

first: Monica

last: Rivera

first: Lucas

middle: F

last: Loffredo

first: Maye

last: Cheng

first: Yinuo

last: Jin

first: Noah

last: Chen

first: Kenia

last: de los Santos-Alexis

first: Elham

last: Azizi

first: Anjali

last: Saqi

middle: B

last: Buchler


title: Mapping the Dialogue: Decoding Alveolar Stem-Niche Interactions [II]

status: Public on Jun 29 2026

city: South San Francisco

first: Anne

last: Biton

state: CA

address: 1 DNA way

country: USA

institute: Genentech

summary: Cellular atlases reveal diverse cellular phenotypes, but how cells traverse this phenotypic landscape to impact tissues requires systematic study. We present an alveolosphere screening platform for investigating interactions between lung epithelial stem cells and their fibroblast niche. We assessed the role of 201 candidate genes in stem cells via imaging, then used RNAseq analysis for a transcriptome-wide understanding of cell-autonomous effects on stem cells and non-cell-autonomous effects on the niche. This phenome-transcriptome map uncovered new cellular states and pathways regulating stem cell growth, metabolism, and immune signaling. Notably, stem cells influenced scar-forming and immune programs in fibroblasts. This injury response was dependent on stem cell identity; loss of Nkx2.1, the transcription factor conferring lung epithelial identity, disrupted stem cell-niche interactions and had a greater non-cell-autonomous effect than eliminating the cancer genes Trp53, Egfr, or Cdkn2b. Our study highlights how functional atlases complement the cellular diversity revealed by descriptive methods.

overall_design: A CRISPR KO screen was conducted in lung alveolar type 2 (AT2) cells. Lung AT2 cells are the progenitors of AT1 cells, responsible for gas exchange in our lung alveoli. After nucleofection of these cells with RNP for our gene of interest, they are co-cultured in Matrigel with human normal lung fibroblasts for 2 weeks. During this time, AT2 cells proliferate, organize into organoid and differentiate. After 2 weeks, RNA is extracted for transcriptomics analysis. RNA was extracted from each well and prepared using SmartSeq3 pipeline. Each fastq file contains reads from both mouse AT2 cells and human fibroblasts.

first: Ahmad

middle: N

last: Nabhan

first: Alina

middle: A

last: Alam

first: Christine

last: Everett

first: Conrad

last: Foo

first: Diana

last: Wu

first: Joshua

middle: D

last: Webster

first: Shiqi

last: Xie

first: Celine

last: Eidenschenk

first: Kim

last: Newton

first: Joseph

middle: R

last: Arron

first: Vishva

middle: M

last: Dixit


title: bulk ATACseq of Ccd18-Co cell line treated with cytokine mix and/or Belinostat

city: Cambridge

first: Simon

last: Koplev

address: Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Puddicombe Way

department: Cambridge Stem Cell Institute

country: United Kingdom

institute: University of Cambridge

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Ccd18-Co cell line unstimualted or stimulated with cytokines, followed by vehicle or epigenetic modulators. N=6 replicates per treatment group.

first: Matthias

last: Friedrich


title: Epigenetic reprogramming of stromal cell states underpins pathologic tissue niches in Crohn’s disease

type: Expression profiling by high throughput sequencing

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

overall_design: Refer to individual Series

first: Fiona

last: Powrie


title: A novel CAF population coordinates hyper-suppressive regulatory T cell recruitment and localization in lung cancer [bulkRNA-seq_Tregs]

city: New York

first: Nicholas

last: Arpaia

overall_design: C57B6/JN mice (n=3) were intravenously injected with 1.5e5 LLC-GFP cells. After 17 days, lungs of mice were harvested. Tumor tissue was collected using mirodissection techniques and digested. Treg cells (FOXP3+ CD4+ TCRb+) were enriched for using a magnetic bead negative enrichment protocol and FACS sorted into Trizol LS based on expression of CXCR3 (CXCR3- or CXCR3+ Treg cells)

first: Olivia

last: Ringham

first: Monica

last: Rivera

first: Lucas

last: Loffredo

first: Maye

last: Cheng

first: Yinuo

last: Jin

first: Noah

last: Chen

first: Kenia

last: de los Santos-Alexis

first: Elham

last: Azizi

last: Saqi

first: Matthew


title: A novel CAF population coordinates hyper-suppressive regulatory T cell recruitment and localization in lung cancer [scRNA-seq_all_cells]

overall_design: C57B6/JN mice (n=3) were intravenously injected with 1.5e5 LLC-GFP cells. After 17 days, lungs of mice were harvested. Tumor tissue and normal-adjacent lung tissue were seperated utilizing microdissection techniques and each tissue was labeled using seperate hashtag oligos (HTOs; (n=6)). Cells were then sequenced using the 10X illumina platform

first: Anjali

last: Buchler


title: A novel CAF population coordinates hyper-suppressive regulatory T cell recruitment and localization in lung cancer [Spatial Transcriptomics]

overall_design: C57B6/JN mice (n=3) were intravenously injected with 1.5e5 LLC-GFP cells. After 17 days, lungs of mice were harvested and flash frozen in OCT. Lungs were then sectioned at 8um thickness onto the 10X visium slide


title: A novel CAF population coordinates hyper-suppressive regulatory T cell recruitment and localization in lung cancer


title: Mapping the Dialogue: Decoding Alveolar Stem-Niche Interactions [I]

first: Anne

last: Biton

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: A CRISPR KO screen was conducted in lung alveolar type 2 (AT2) cells. Lung AT2 cells are the progenitors of AT1 cells, responsible for gas exchange in our lung alveoli.  After nucleofection of these cells with RNP for our gene of interest, they are co-cultured in Matrigel with human normal lung fibroblasts for 2 weeks. During this time, AT2 cells proliferate, organize into organoid and differentiate. After 2 weeks, RNA is extracted for transcriptomics analysis.  RNA was extracted from each well and prepared using SmartSeq3 pipeline. Each fastq file contains reads from both mouse AT2 cells and human fibroblasts.

first: Ahmad

last: Nabhan

first: Alina

last: Alam

first: Christine

last: Everett

first: Conrad

last: Foo

first: Diana

last: Wu

first: Joshua

last: Webster

first: Shiqi

last: Xie

first: Celine

last: Eidenschenk

first: Kim

last: Newton


title: Comprehensive spatial profiling of the spleen in human myelofibrosis [ST_Visium]

city: Pessac

first: Bérénice

last: Dugué

address: 1 Av. Magellan

country: France

institute: INSERM

summary: Splenomegaly is a defining feature of myelofibrosis, yet the contribution of splenic mesenchymal stroma to disease progression remains unclear. We combined spatial and single-nucleus transcriptomics of patient spleens to map extramedullary hematopoiesis niches. Activated red pulp reticular cells localize near hematopoietic stem and progenitor cells, and early disease shows marginal zone disruption with lymphoid depletion preceding stromal remodeling. Macrophage- and megakaryocyte-derived signals activate complement and induce TNFα, TGF-β, extracellular matrix, and Thbs1 programs in reticular cells.

overall_design: Visium Spatial Transcriptomics and Single-Nuclei profiling of human spleens of patients with myelofibrosis

first: Pia

last: Wanner

first: Mayra

last: Ruiz Tejada Segura

first: Mohamed

last: Saad

first: Lucas

last: Greven

first: Katrin

last: Gotz

first: Carmen

last: Schalla

first: Stijn

last: Fuchs

first: Gerjanne

last: Vroeg in de wei

first: Hélène

last: Gleitz

first: Anna Katharina

last: Galyga

first: Jessica

last: Ellen Pritchard

first: Tobias

last: Schlangen

first: Niklas

last: Lutterbach

first: Salim

last: Atakhanov

first: Lina

last: Schmidt

first: Marie

last: Parrens

first: Armelle

last: Peyrat

first: Damien

last: Luque Paz

first: Marie-Christine

last: Copin

first: Alexandre

last: Guy

first: Victor-Emmanuel

last: Brett

first: Olivier

last: Mansier

first: Susanne

last: Schmitz

first: Paul

last: Wanek

first: Bella

last: Banjanin

first: Stephani

first: Martina

last: Crysandt

first: Marian

last: Clahsen-van Groningen

first: Konnie

last: Hebeda

first: Sascha

last: Dietrich

first: Harald

last: Voehringer

first: Matthias

last: Meyer-Bender

first: Kristin

last: Séré

first: Chloé

last: James

first: Adam

last: Benabid

first: Ivan

last: Costa

first: Charles

last: Dussiau

first: Rebekka

last: Schneider


title: Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling

city: Stony Brook

first: Maurizio

last: Del Poeta

state: NY

address: 150 Life Science Building

department: Molecular Genetics and Microbiology

institute: Stony Brook University

summary: Cryptococcosis is a life-threatening fungal disease caused by Cryptococcus neoformans. The immunocompetent response results in the formation of a lung granuloma, which contains the fungal cells. We have previously developed a mouse model of the cryptococcal granuloma that is histological similar to the human lung granuloma. In this study, we characterize the lung granuloma in mice using transcriptomics and lipidomics, elucidating the immune cell types present and the transcriptional landscape of macrophages at the granuloma border. Macrophage subtypes are identified, which form a characteristic boundary of the lung granuloma and were observed to have differentially expressed genes involved in the control of the infection. Lipidomic studies revealed that several sphingolipid-associated genes and their products involved in the regulation of phagocytosis were found to be upregulated and in vivo validation studies confirmed their key role in granuloma formation. Lastly, as the granuloma structure develops, the fungal replication inside the granuloma decreases concomitantly to the decrease of the macrophage activation. These studies identified important immune mechanisms of host protection at the granuloma site. Our results provide mechanistic insight into cryptococcal granuloma maturation and refine current models of host–pathogen interaction, which may open avenues for future immunomodulatory strategies

overall_design: Mice are infected with a mutant strain of Cryptococcus neoformans (Δgcs1), which allows for the granulomatous response. Cells were collected from the granuloma at three time points (30, 60, and 90 days-post-infection), as well as from WT-infected and uninfected controls, and were then analyzed via scRNA-seq

first: Veronica

last: Soares Brauer

first: Kathryn

last: Takemura

first: Barbara

last: Rosati

first: Marinaldo

last: Pacífico Cavalcanti-Neto

first: Deveney

last: Dasilva

first: Neelu

last: Singh

first: Tyler

last: Normile

first: Gabriella

last: Vaccaro

first: Guiseppe

last: Caso

first: Harpreet

first: Bo

last: Chen

first: Iwao

last: Ojima

first: David

last: McKinnon


title: Independent cell type-specific expression and distal regulation of the 9p21 locus cell cycle regulators: p14ARF, p16INK4A, p15INK4A, and ANRIL [CRISPR and scRNA-seq]

first: Neva

middle: Cherniavsky

last: Durand

state: MA

address: 75 Ames St

institute: Broad Institute

summary: The 9p21 locus encodes tumor suppressors p16INK4A and p14ARF (both encoded by CDKN2A), p15INK4B (CDKN2B), and a long non-coding RNA, ANRIL (CDKN2B-AS1). The ~1 megabase locus is notable for a high density of single nucleotide polymorphisms (SNPs) associated with aging-related diseases and traits. Despite clear importance, our understanding of the the cell-type specific expression dynamics and cis-regulatory mechanisms of the 9p21 transcripts has been constrained by the complexity of the transcript structures, low expression, and severe alterations to the locus in cancer cell lines. Here, we innovated custom computational and molecular tools to overcome these technical challenges and fill critical knowledge gaps in our understanding of 9p21 locus architecture and regulation of the 9p21 transcripts. Across tissues, we found that p15INK4b is the predominant transcript. We deconvolved the expression of the CDKN2A transcripts, p16INK4A and p14ARF, revealing stark differences in the expression of these overlapping but functionally distinct transcripts across tissues and cell types. Comparative analysis in a model of fibroblast senescence revealed a striking switch from preferential p14ARF expression in cycling cells, to p16INK4A and p15INK4b as cells age and senescence. Perturbation of putative cis regulatory elements nominated a network of promoters and enhancers that regulate p16INK4A, p14ARF, and p15INK4b and ANRIL. The identified elements are accessible in vivo, and can be used to guide studies into variant interpretation. Our systematic characterization of 9p21 transcript isoforms, promoters, and distal elements across cell states, in vivo tissues and senescence offers new mechanistic insights and a framework for future studies of this vital but poorly understood locus.

overall_design: This study systematically profiles the 9p21 locus to dissect transcript expression, chromatin architecture, and regulatory element function across multiple experimental modalities. Dial-up scRNA-seq (Gray et al. and Chan et al.) captures per-cell transcript expression, including new experiments outside published datasets. Region Capture Micro-C (RCMC) maps 3D chromatin contacts at the locus. ChIP-seq for CTCF and H3K27ac identifies regulatory protein binding and active enhancer marks. A pooled CRISPRa screen with CROP-seq and single-cell RNA-seq tests candidate regulatory elements for effects on gene expression. Complementary total RNA-seq in WI-38 cells across senescence provides temporal expression dynamics. Reference and supporting files, including custom annotations and curated target region sets, facilitate reproducibility and interpretation.

first: Elena

last: Torlai Triglia

middle: E

last: Miller

middle: C

first: Kyung Lock

last: Kim

first: Salva

last: Casani Galdon

first: Joshua

last: D’Antonio

first: Noam

last: Shoresh

first: Kristin

last: Ardlie

last: Hendrickson

first: J Graham

last: Ruby

first: Bradley

last: Bernstein

first: Elizabeth

last: Gaskell


title: Myeloid-avid mTOR-inhibiting nanobiologic attenuates allograft fibrosis after lung transplantation

city: St Louis

first: Junedh

last: Amrute

state: MO

address: 660 S Euclid Ave

institute: Washington University School of Medicine

summary: Chronic lung allograft dysfunction (CLAD) is characterized by fibrotic graft remodeling and limits long-term survival after pulmonary transplantation. Despite clinical evidence that myeloid cells drive conditions that increase the risk of CLAD development, contemporary immunosuppression primarily target lymphocytes. We evaluated an mTOR inhibiting nanobiologic (mTORi-NB) targeting myeloid cells and their progenitors in a semi-allogeneic mouse model of CLAD. We found that the mTORi-NB preferentially targeted myeloid and endothelial cells in the allografts. Brief peri-operative therapy with the mTORi-NB reduced early macrophage graft infiltration and inhibited acute inflammation. In mTORi-NB-treated lung recipients, transcriptomic analysis revealed downregulation of fibrotic genes in macrophages and type I (AT1) and type II (AT2) alveolar epithelial cells, known drivers of pulmonary fibrogenesis. We also observed upregulation of anti-fibrotic genes in macrophages after treatment with mTORi-NB, as well as reduction of allograft fibrosis, associated with preservation of AT2 cells. Our findings suggest that myeloid-avid immunosuppression may be a promising approach for inhibiting CLAD.

overall_design: Lung tissue digestion and single cell suspension preparation were performed as previously described (doi:10.1016/j.ajt.2025.08.021). Two lungs were pooled from each group at day 14 post-transplant. Samples were submitted to the Washington University Genome Technology Access Center for single nuclear genome-scale metabolic model and library construction.

first: Katsutaka

last: Mineura

first: Charles

last: Liu

first: Shinichi

last: Kawana

first: Fatima

last: Elmenshawy

first: Jonathan

last: Perez

first: Will

last: Lounsbery-Scaife

first: Nikita

last: Poddar

first: Venkatrao

last: Nunna

first: Wenjun

last: Li

first: Yuriko

last: Terada

first: Austin

last: Meadows

first: Gyu Seong

last: Heo

first: William

last: Wang

first: Maria Gulia

last: Davighi

first: Judit

last: Morla-Folch

first: Seokchan

last: Park

first: Gabriel

last: Laghlali

first: Eleanor

last: Burgess

first: Michael

last: Schotsaert

first: Yongjian

first: Kory

last: Lavine

first: Jon

last: Ritter

first: Vibha

last: Lama

first: Steven

last: Brody

first: Ruben

last: Nava

first: Andrew

last: Gelman

first: Alexander

last: Krupnick

first: Leticia

last: Perez-Rodriguez

first: Dan

last: Hasson

first: Abraham

last: Teunissen

first: Jordi

last: Ochando

first: Daniel

last: Kreisel


title: Temporal Uncoupling of Radial Glial Progenitor Cell Lineage Progression in Self-organizing Organoid System – mTmG scRNA-Seq

city: Klosterneuburg

first: Florian

last: Pauler

address: Am Campus 1

country: Austria

institute: Institute of Science and Technology Austria (IST Austria)

summary: Radial glial progenitors (RGPs) produce all excitatory neurons in the developing cerebral cortex. Mosaic Analysis with Double Markers (MADM)-based lineage tracing in vivo revealed a quantitative framework of RGP lineage progression. Here we established MADM technology in embryonic stem cells to probe RGP lineage progression in self-organizing cortical organoid system. We found that RGPs exhibit high level of equipotency in organoid rather than temporally stereotyped lineage progression as observed in vivo. RGPs in organoids showed increased lineage restriction, diminishing cell-type diversity in clones of cortical projection neurons, despite uniform RGP scRNAseq transcriptional signatures and unitary lineage trajectory. Hence, critical non-cell-autonomous cues absent in self-organizing systems and/or genuine stem cell niche are essential for faithful RGP lineage progression and the generation of cortical cell-type diversity.

overall_design: Single cell RNA-Seq of cortical organoids and in vivo cortical tissue from mice with with mTmG; Emx1-Cre transgenes to label all Cre-expressing cells with GFP (green) in a tdT (red) background.

first: Melissa

last: Stouffer

first: Giselle

last: Cheung

first: Simon

last: Hippenmeyer


title: H3K4me3 CUT&RUN profiling of MCF7 parent cells following abemaciclib treatment

city: Melbourne

first: Shom

last: Goel

state: Victoria

address: 305 Grattan St

country: Australia

institute: Peter MacCallum Cancer Centre

summary: The retinoblastoma protein (Rb) is a tumour suppressor best known for repressing E2F transcription factors and halting cell cycle progression. In hormone receptor-positive (HR+) breast cancer, CDK4/6 inhibitors activate Rb by preventing its phosphorylation, forming a key component of current endocrine therapy regimens. How pharmacologically activated Rb remodels chromatin and influences transcription beyond cell cycle arrest remains poorly understood. Here we show that CDK4/6 inhibition induces redistribution of hypo-phosphorylated Rb to promoters and enhancers. While Rb predictably binds to cell cycle gene promoters to repress transcription, at other sites it unexpectedly promotes expression of oestrogen-responsive genes by integrating into oestrogen receptor (ER)-rich transcriptional hubs. CDK4/6 inhibition enhances ER target gene expression in breast cancer cells, patient-derived xenografts, and clinical HR+ breast cancer samples in an Rb-dependent manner. This reprogramming is mediated in part by KDM5A, whose interaction with Rb contributes to gene regulation at these loci. Critically, components of this Rb-driven ER transcriptional program are pro-proliferative. In endocrine-sensitive tumours, this can be neutralised with anti-oestrogen therapy, explaining therapeutic synergy. In endocrine-resistant settings such as ESR1-mutant breast cancer, the program persists, limiting therapeutic efficacy. These findings reframe Rb as a dual-function transcriptional regulator that, while enforcing cell cycle arrest, can also activate programs that counteract its tumour suppressor function.

overall_design: CUT&RUN for H3K4me3 in estrogen receptor-positive cell line MCF7 treated with DMSO control or abemaciclib 500 nM for 5 days. Two replicates per group.


title: KRT6A enhances radiotherapy resistance in lung squamous cell carcinoma via activation of the autophagy pathway through RAB39B [RNA-Seq 1]

city: Dalian

first: Dachuan

last: Shen

address: No. 10, Xuefu Street, Dalian Economic and Technological Development Zone

country: China

institute: Dalian University

summary: Abstract  Background: Radiotherapy is the cornerstone for lung squamous cell carcinoma (LUSC) treatment, yet its efficacy is often limited by the development of radioresistance. Understanding the molecular mechanisms driving this resistance is critical for improving therapeutic outcomes. Results: In this study, we established a radioresistant LUSC cell line and identified KRT6A as a pivotal gene involved in radiotherapy resistance. Transcriptome sequencing and further validation revealed RAB39B as a downstream target of KRT6A. The KRT6A-RAB39B axis promotes radioresistance by activating the autophagy pathway, enhancing cancer cell survival in response to radiation stress. Mechanistic studies confirmed that KRT6A regulates autophagy through modulation of RAB39B expression. Conclusions：This work is the first to uncover a role of the KRT6A-RAB39B axis in LUSC radioresistance, offering new insights into the mechanisms and potential targets underlying radiotherapy failure.

overall_design: Total RNA was extracted from SK-MES-1 cells with transient KRT6A knockdown and the control cells and subjected to RNA-seq.

first: Zaishuang

last: Ju

first: Yutong

last: Wu

first: Zhiqi

last: Zheng

first: Eric

middle: W

last: Lam

first: Ruoyu

last: Wang


title: Histamine H4 receptor antagonists prevent receptor-mediated and EBV-induced B cell proliferation [ATAC-seq]

city: Oullins

first: Fabrice

last: Chatonnet

address: 165 Chemin du Grand Revoyet

summary: Epstein-Barr virus (EBV) infects over 90% of the global population and establishes lifelong latency in memory B cells. In healthy individuals, this latent infection is typically kept in check by the immune system. However, in immunosuppressed patients, EBV can reactivate, leading to uncontrolled B cell proliferation and development of post-transplant lymphoproliferative disorders (PTLD)—a potentially fatal complication. In this study, we demonstrate that selective antagonists of the histamine H4 receptor (H4R), a G protein-coupled receptor expressed in immune cells, potently suppress B cell activation and proliferation triggered by antigenic stimuli or EBV infection. Notably, the lead compound A943931 inhibited transcriptional programs critical for B cell activation, including downregulation of key metabolic genes, resulting in profound suppression of both glycolysis and oxidative phosphorylation. A943931 also blocked EBV-driven B cell immortalization and impaired energy metabolism in lymphoblastoid cell lines, albeit to a lesser extent than in receptor-stimulated B cells. In vivo, A943931 suppressed tumor growth in Daudi Burkitt lymphoma xenografts and prevented B cell lymphoma development in EBV-infected humanized mice. These findings reveal a novel immunometabolic vulnerability of EBV-infected B cells and position H4R antagonists as promising therapeutic candidates for EBV-associated lymphoproliferative disorders, including PTLD and potentially EBV-linked autoimmune diseases.

overall_design: Chromatin accessibility was assessed by ATAC-seq on purified CD19+ B cells from five blood donors, seeded at a density of 106 cells per ml in complete RPMI 1640 medium, supplemented with GlutaMAX, 10% heat-inactivated FCS, 100 U/ml penicillin, 100 μg/ml streptomycin, and then stimulated with 5 μg/mL CpG-B ODN2006 and 10 μg/mL anti-Human IgG + IgM (H+L) for 24 h. Simultaneously, purified CD19+ B cells were mock-treated with DMSO or treated with A943931 at 10 μM. Genome-wide chromatin accessibility profile was obtained using the FAST-ATAC published protocol (Corces et al., Nature Genetics, 2016) for live sorted cells with a few adaptations.

first: Marlène

last: Roy

first: Émilie

last: Bardel

first: Amel

last: Chebel

first: Pierre-Olivier

last: Vidalain

first: Patrice

last: André

first: Laurent

last: Genestier


title: Persistent chromatin alterations and gene expression reprogramming follow widespread DNA damage in glioblastoma [RNA-Seq]

city: Los Angeles

first: Aram

last: Modrek

state: Ca

address: 1441 EastLake Ave

institute: USC

summary: We introduced hundreds of CRISPR–Cas9-mediated DNA double-strand breaks (DSBs) into glioblastoma stem-like cells and tracked chromatin, transcriptional, and structural changes over time. Long after the DSBs were repaired, we found durable reprogramming of chromatin conformation and gene expression, as well as emergence of structural variants. These findings suggest that DNA damage can induce stable non-genetic alterations in cancer cells.

overall_design: Hi-C was performed in glioblastoma stem-like cells treated with doxycycline-inducible multi-target gRNAs (mtg142 or mtg483) to introduce widespread DSBs. Samples were collected at 3 hours and 2 weeks post-induction. Vector control cells (wtCas9 expressed with no guide RNA) were also included. Each condition was run in biological duplicate.

middle: S

first: Keerthivasan

last: Chandradoss

first: Catherine

last: Do

first: Ravesanker

last: Ezhilarasan

first: Theodore

last: Sakellaropoulos

first: Jerome

last: Karp

first: Yingwen

last: Ding

first: Ze-Yan

last: Zhang

first: Melanie

last: Graciani

first: Giulia

last: Cova

first: Jennifer

last: Phillips-Cremins

first: Erik

middle: P

last: Sulman

first: Jane

last: Skok


title: Targeting palmitoylation enhances neutrophil-mediated cancer cell killing in liver metastases [scRNA-seq]

city: Leuven

first: Juan

last: Fernández-García

address: Campus Gasthuisberg, O&N4, Herestraat 49, box 912

department: VIB-KU Leuven Center for Cancer Biology

country: Belgium

institute: VIB/KU Leuven

summary: Liver metastases are frequent and challenging to treat as the liver is a metabolically highly active and immune-tolerant organ. However, how cancer cells exploit the nutrients available in the liver to further exacerbate evasion from the immune system remains largely unknown. We discovered that palmitate availability in the liver promotes neutrophil extracellular traps (NETs) in the presence of cancer cells. Mechanistically, we found that liver metastases from breast and colorectal cancer require the palmitoyltransferase 17 (DHHC17, gene name ZDHHC17) to secrete laminin-511. In turn, neutrophils in the liver metastasis environment responded to laminin-511 by increasing NETosis and decreasing their cancer cell killing capacity. In line, we observed that silencing ZDHHC17 in cancer cells decreased metastasis growth only in the presence of neutrophils, while metastasis growth was rescued in ZDHHC17-silenced metastases upon injection of laminin-511 or inhibition of neutrophil degranulation. Taken together, we found that liver palmitate not only aids cancer cell intrinsic processes but it also enables cancer cells to evade neutrophil destruction.

overall_design: Single-cell RNA-seq profiling of liver metastases originating from control (shSCR) and ZDHHC17-silenced (shZdhhc17) 4T1 murine triple-negative breast-cancer cells, dissected at Day 14 after intrasplenic injection into 6-8 week-old female BALB/c mice.

first: Anke

last: Vandekeere

first: Sarah

last: Fendt


title: Transcriptomic analysis of human small intestinal organoids (hSIOs) from PiMM and PiZZ patients

city: Pozzuoli

first: Rossella

last: De Cegli

address: Via Campi Flegrei 34

country: Italy

institute: Tigem

summary: Transcriptomic analysis was performed on human small intestinal organoids (hSIOs) generated from induced pluripotent stem cells (iPSCs) from PiMM and PiZZ patients. This analysis revealed that accumulation of mutant Z alpha1 antitripsin in intestinal cells induces activation of pathways related to stress, including protein processing in ER and immune response, while dowregulates the expression of genes related to cell cycle, DNA repair, and stemness.

overall_design: Total RNA was extracted from n=4 hSIOs from PiMM and n=5 hSIOs from PiZZ patients.

first: Nunzia

last: Pastore

first: Francesco

last: Annunziata


title: Targeting palmitoylation enhances neutrophil-mediated cancer cell killing in liver metastases [RNA-seq]

overall_design: RNA-seq profiling of liver metastases originating from control (shSCR) and ZDHHC17-silenced (shZdhhc17) 4T1 murine triple-negative breast-cancer cells, dissected at Day 10 after hydrodynamic injection into 6-8 week-old female BALB/c mice.


title: Accumulation of mutant Z α1-Antitrypsin impairs intestinal function in mice

summary: We found that accumulation of mutant Z α1-Antitrypsin in intestinal cells, and in particular in Paneth cells, induces activation of proteotoxic pathways leading to impaired intestinla homeostasis in PiZ mice.

overall_design: Total RNA was extracted from n=4 for each experimental group: Transcriptomic analysis was performed on intestine from WT and PiZ mice collected at 6 weeks of age.

first: De Cegli

last: Rossella

first: Pastore

last: Nunzia

first: Annunziata

last: Francesco


title: BMAL1 and YAP cooperate to hijack enhancers and promote inflammation in the aged epidermis

city: Barcelona

first: Camille

last: Stephan Otto Attolini

state: Select a State or Province

address: Baldiri Reixac 10

department: Biostatistics and bioinformatics Unit

country: Spain

institute: IRB Barcelona

overall_design: Refer to individual Series


title: Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [RNA-Seq]

city: La Jolla

first: Brian

last: Yee

address: 9500 Gilman Dr

department: Health

institute: UCSD

summary: Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates transcript isoforms with distinct 3' ends. While several RNA-binding proteins (RBPs) are known to regulate APA, the roles of the vast majority of RBPs in this process remain poorly characterized. Using a large-scale tethered function assay, we screened a library of 879 human RBPs to identify regulators of APA. We discovered 52 RBPs that modulate APA, validated their functions through knockdown PAS-seq and enhanced crosslinking and immunoprecipitation (eCLIP), and developed a fine-tuned transformer model to predict activators of PAS selection. We focused on two unexpected hits: GRB2, an adaptor protein with crucial roles in cell signaling, and RNPS1, a member of the exon junction complex (EJC). We uncovered mechanisms by which they modulate APA using affinity purification mass spectrometry (AP-MS) and biochemical assays. Our screen provides a comprehensive resource of RBPs involved in APA and reveals unexpected roles of signaling factors in APA regulation.

overall_design: shRNA knockdown bulk RNA-seq of target RBP  and non-targeting controls in HEK293T cells without additional treatment. Groups correspond to the non-targeting controls against which knockdown samples were compared against

first: Pratibha

last: Jagannatha

first: Yoseop

last: Yoon

first: Samuel B.

last: Landy

first: Jack T.

last: Naritomi

first: Lijun

last: Zhan

first: Sara

last: Olson

first: Xintao

last: Wei

first: Lena A.

last: Street

first: Liang

last: Liu

first: Joshua

last: Jeong

first: Jack

last: Reid

first: Lindsey V.

last: Soles

first: Elijah K.F.

last: Rosales

first: Vicky W.

last: Chen

first: Shuhao

last: Xu

first: Avery

last: Pong

first: Marko

last: Jovanovic

first: Brenton R.

last: Graveley

first: Yongsheng

last: Shi

first: Gene W.

last: Yeo


title: Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection

city: Irvine

first: Yoseop

last: Yoon

address: 1002 Health Sciences Rd

institute: University of California Irvine

summary: Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates transcript isoforms with distinct 3' ends. While several RNA-binding proteins (RBPs) are known to regulate APA, the roles of the vast majority of RBPs in this process remain poorly characterized. Using a large scale tethered function assay, we screened a library of 879 human RBPs to identify regulators of APA. We discovered 52 RBPs that modulate APA, validated their functions through knockdown PAS-seq and enhanced crosslinking and immunoprecipitation (eCLIP), and developed a fine-tuned transformer model to predict activators of PAS selection. We focused on two unexpected hits: GRB2, an adaptor protein with crucial roles in cell signaling, and RNPS1, a member of the exon junction complex (EJC). We uncovered mechanisms by which they modulate APA using affinity purification mass spectrometry (AP-MS) and biochemical assays. Our screennprovides a comprehensive resource of RBPs involved in APA and reveals unexpected roles of signaling factors in APA regulation.

overall_design: To determine whether the RBP candidates identified from the screen regulate APA of genes in their endogenous context, we depleted these proteins using RNAi and performed PAS-seq to quantify APA transcriptome-wide


title: Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [eCLIP]

first: Brian

last: Yee

overall_design: Enhanced immunoprecipitation and crosslinking followed by sequencing( eCLIP) data generated for candidate RBPs in HEK293T cells. No additional treatment conditions were used in the experiment.

first: Pratibha

last: Jagannatha

first: Samuel B.

last: Landy

first: Jack T.

last: Naritomi

first: Lijun

last: Zhan


title: Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements

city: Shanghai

first: Yu

last: Liang

address: Yueyang Road 320

department: SIBCB

institute: CEMCS, CAS

sample_organism:
Drosophila melanogaster
Mus musculus

platform_organism:
Drosophila melanogaster
Mus musculus

first: Yi Ni

last: Luo

first: Shuheng

last: Wu

first: Yazi

last: Deng

first: Wei

first: Z.Z. Zhao

last: Zhang

first: Lu

last: Wang


title: Shaping Gut Immunity with Intestinal Epithelial-Immune Dynamics in Peyer's Patches.

city: Brisbane

first: M. Zeeshan

last: Chaudhry

state: Queensland

address: 37 Kent Street

institute: The University of Queensland

summary: Microfold (M) cells are specialized antigen-sampling cells that transcytose luminal antigens to underlying immune cells to initiate mucosal immunity. How they are programmed in different intestinal tissues and their role during enteric infections has not been resolved. Here, we demonstrate that M cells are critical for B cell activation and IgA production that shapes the intestinal microbiome and maintains steady-state intestinal epithelial integrity. Tuft cells and M cells share expression of SPI-B. Molecular mapping revealed that M cells exhibit significant heterogeneity including tissue-specific and pathogen-specific tailored programs. These include key pathways regulating fatty acid uptake and metabolism in the intestinal epithelium. Confocal imaging demonstrated that Peyer’s patch SPI-B+ M cells act to retain group 3 innate lymphoid cells and IL-22 production within the Peyer's patch epithelium. By identifying interconnected cellular and molecular programs, we uncover novel spatially organized immune-epithelial regulatory networks essential for immune protection.

overall_design: CD45-EpCAM+SPI-B-tdTomato+ IECs (15,593 cells) isolated from Peyer’s patches of Spib-tdTomatox Rorc-gfp/+ mice  were flow cytometrically sorted and processed as one GEM-X sample. The immune cell population from Peyer’s patches of Spib-tdTomatox Rorc-gfp/+ mice consisted of CD45+lineage-CD90.2+RORgt-GFP+ cells (ILC3, 2,118 cells ) that were mixed with CD45+GFP- cells (4,000 cells) and processed in one well of GEM-X 3' Chip. The libraries were prepared with 10x GEM-X v4 kit.

first: M Zeeshan

first: Wang

last: Cao

first: Gabrielle

last: Belz


title: Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements [Nanopore]

summary: While the resurrection of transposons is tightly linked with cancer, neurodegenerative disorder and other pathologies, the precise suppression mechanisms and mobilization events of transposons during somatic development remain largely obscure. Here, we present a highly conserved mechanism that prevents transposon activation and mobilization. By tracking transposition events, we identified that Cramp1 plays a pivotal role in safeguarding both Drosophila and mouse development through silencing transposon mobility. Cramp1 was characterized as a major factor that specifically binds to the DNA sequences of histone gene cluster through its SANT domain, thereby initiating his1 transcription. The linker protein H1 then physically interacts and recruits Nsd to catalyze H3K36 dimethylation, which subsequently promotes proper deposition of both H4K20m3 and H3K9me3 to H3K36me2 established heterochromatin region for transposon silencing. In the absence of Cramp1 protection, uncontrolled transposons will induce massive DNA breaks, leading to abnormal hindgut regeneration in Drosophila and disrupted embryonic erythropoiesis in mice. Our finding highlights the endless arms race between hosts and transposons happening during evolution, wherein the key factors also evolve to suppress transposon mobilizations during somatic development.

overall_design: We employed Nanopore sequencing to capture the bona fide mobilization events within Drosophila hindguts and RNA-seq and scRNA-seq to quantify transposon expression. Combined with END-seq and ChIP-seq, we were able to gain a comprehensive understanding of the breakpoints generated at transposon insertion sites and the changes in histone modifications on the transposons.

first: Yini

first: ZZ

middle: Z


title: Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements [RNA-seq]


title: Reciprocal genetic screens identify epigenetics factors controlling epidermal cell activation.

city: Turin

first: Andrea

last: Lauria

address: Via Accademia Albertina, 13

department: Life Sciences and Systems Biology

institute: University of Turin

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


title: Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements [scRNA-seq]


title: Unraveling the Spatial Dynamics of Immune-Epithelial Interactions in the Intestinal Tract

summary: Intetsinal epithelium is the frontline of the gut mucosal barrier and consists of diversified epithelia cells playing different rols in the host defense against invading microorgansiums. Here, we studied the Microfold (M) cells located in the different regions of the intestine and generated a blueprint of M cells, in particular their gene expression and matuation programs. M cells, under steady state and the stress of pathogen (Salmonella or Citrobactor) invasion, were shown to have distinct gene expression profiles, highlighting their roles in denfensing different pathogens.

overall_design: Intestinal epithelial cells were isolated from naïve, Salmonella or Citrobactor infected were isolated and single cell sequenced to acquire their gene expression profiles.

first: Yue

last: You

first: Peter

last: Hickey

first: William

last: Ho


title: Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements [ChIP-seq]

first: Yu


title: Stress-Coping Phenotypes Shape Adipose Tissue Function and Plasticity and Modulate Metabolic Resilience

status: Public on Jun 28 2026

city: Ariel

first: Tovit

last: Rosenzweig

address: 3 Kiryat HaMada St.

country: Israel

institute: Ariel University

summary: This study investigated how stress-coping phenotypes (stress-resilient Dominant and stress-vulnerable Submissive mice) shape white adipose tissue (WAT) function under standard and high-fat diet (HFD) conditions. Metabolic, molecular, and transcriptomic analyses were performed on epididymal (eWAT) and inguinal (iWAT) white adipose tissue. Results revealed that stress-vulnerable mice exhibit impaired adipogenesis, adipocyte hypertrophy, unfavorable adipokine profiles, and defective insulin signaling in WAT under HFD. Transcriptomic profiling by RNA-seq identified adipogenesis, fatty acid metabolism, and oxidative phosphorylation as differentially regulated pathways between the strains. Functional analyses confirmed reduced proliferative and adipogenic potential of stromal vascular fraction (SVF) cells from stress-vulnerable mice. Pharmacological activation of PPARgamma (pioglitazone) improved adipogenesis and metabolic parameters, while antidepressant treatment (paroxetine) normalized behavioral deficits and improved adipogenic capacity in stress-vulnerable mice.

overall_design: RNA-seq profiling of iWAT and eWAT from stress-resilient (Dominant) and stress-vulnerable (Submissive) male mice fed standard diet (STD) or high-fat diet (HFD) for 8 weeks.

first: Saumya

last: Mehta

first: Michaella

last: Ben-Shachar

first: Sharmila

last: Govindaraj

first: Suparna

last: Sen

first: Adrian

last: Segev

first: Oshrit

last: Rahimi

first: Valid

last: Gahramanov

first: Galia

last: Luboshits

first: Michael

last: Firer

first: Ayala

last: Wollman

first: Albert

last: Pinhasov


title: Transcriptomic profiling of upper incisor tissues from neural crest-specific Alx1 conditional knockout mice at embryonic day 13.5

city: Fuzhou

first: Xi

last: Zheng

address: No.18 Middle Wulongjiang Avenue, Shangjie, Minhou, Fuzhou, Fujian

institute: Fujian Medical University

summary: Tooth morphogenesis depends on reciprocal interactions between the dental epithelium and neural crest-derived mesenchyme. ALX1 is a paired-like homeodomain transcription factor implicated in craniofacial development, yet its molecular function during tooth development remains poorly understood. To investigate the transcriptional changes associated with loss of Alx1 during early odontogenesis, we performed bulk RNA sequencing of upper incisor tissues isolated from embryonic day 13.5 (E13.5) neural crest-specific Alx1 conditional knockout mice (Wnt1-Cre;Alx1 flox/flox) and littermate wild-type controls. This dataset provides a comprehensive transcriptomic resource for identifying genes and signaling pathways regulated by Alx1 during early upper incisor development.

overall_design: Bulk RNA sequencing was performed on upper incisor tissues dissected from embryonic day 13.5 (E13.5) mouse embryos. Samples were collected from neural crest-specific Alx1 conditional knockout mice (Wnt1-Cre;Alx1 flox/flox, n = 3) and littermate wild-type control mice (n = 3). Total RNA extracted from each biological replicate was used for library preparation and paired-end sequencing on an Illumina platform. Differential gene expression analysis was performed to identify transcriptional changes associated with Alx1 deficiency during early upper incisor development.

first: Hongbin

last: Lu

first: Meiyang

last: Chen

first: Ying

last: Xu

first: Chensheng

last: Lin

first: Yi

last: Lv

first: Yanding

last: Zhang

first: Xuefeng

last: Hu

first: Minkui


title: Metabolic stress-induced astrocytic senescence and neurotoxicity are driven by LRRK2-G2019S and reversible by LED Photobiomodulation

city: Incheon

first: jeehoon

last: Lee

country: South Korea

institute: Inha University

summary:
Under metabolic stress, the LRRK2-G2019S mutation accelerates astrocytic senescence by physically sequestering DDB1. This aberrant interaction impedes the CUL4–DDB1-mediated proteasomal degradation of p21, leading to massive p21 accumulation, an exacerbated senescence-associated secretory phenotype (SASP), and subsequent neurodegeneration. Crucially, non-invasive LED-PBM dismantles this pathogenic axis by selectively disrupting the LRRK2–DDB1 interaction, thereby restoring p21 clearance and uncoupling metabolic dysfunction from neuronal injury.
Transcriptomic profiling via microarray was employed to unbiasedly interrogate global gene network alterations driven by the interaction between metabolic stress and the LRRK2-G2019S mutation

overall_design: Whole brains were harvested from LRRK2-wild type (LRRK2-WT) and LRRK2-G2019S (LRRK2-GS) mice maintained on a high-fat diet (HFD) for 12 weeks. Total RNA was isolated using RNAiso Plus and subsequently purified with RNeasy columns. Global gene expression profiling was performed via the Affymetrix Mouse Clariom S Assay in biological triplicate for both the HFD-fed LRRK2-WT (samples wh1–wh3) and LRRK2-GS (samples gh1–gh3) groups

first: Jeehoon

first: Jihye

last: Han


title: DUSP5 regulates ferroptosis in pancreatic cancer by down-regulating SCD1 expression via ERK1/2

city: Shijiazhuang

first: Zhang

last: Zhilei

address: No.12, Jiankang Road, Chang'an District, Shijiazhuang City

institute: The Fourth Hospital of Hebei Medical University

summary: This study aimed to explore the role and mechanism of DUSP5 in pancreatic ductal adenocarcinoma (PDAC). RNA sequencing was performed in DUSP5-overexpressing PANC-1 cells and control cells to identify differentially expressed genes. The results revealed that DUSP5 significantly downregulated stearoyl-CoA desaturase 1 (SCD1), a key enzyme involved in fatty acid metabolism and ferroptosis regulation. Our findings indicate that DUSP5 promotes ferroptosis and suppresses PDAC proliferation through the ERK1/2-SCD1 signaling pathway.

overall_design: This study included transcriptome profiling of DUSP5-overexpressing and control PDAC cells. Human PDAC cell line PANC-1 was used and divided into two groups: empty vector control group (EV) and DUSP5 overexpression group (DUSP5-OE). Each group contained three independent biological replicates. All samples were subjected to whole-transcriptome RNA sequencing to investigate the molecular mechanism by which DUSP5 regulates ferroptosis and tumor proliferation in pancreatic cancer.


title: Development of an Optimized Epigenetic Silencer to Transcriptionally Inactivate Viral DNA in Chronic Hepatitis B [HBVMethylseq]

city: Boston

first: Jennifer

last: Marlowe

state: Massachusetts

address: 201 Brookline Avenue

institute: nChroma Bio

type: Methylation profiling by high throughput sequencing

summary: Approved chronic hepatitis B (CHB) therapies rarely result in functional cure, as they fail to permanently silence all transcriptionally active hepatitis B virus (HBV) DNA. CRMA-1001 employs an optimized epigenetic silencer that represses viral transcription through targeted deposition of DNA methylation on episomal and integrated HBV DNAs. In HBV mouse models, a single dose of CRMA-1001 produced >3 log10 reductions in viral biomarkers, which correlated with de novo methylation of HBV DNA. Three doses resulted in up to 90% of animals with undetectable hepatitis B surface antigen (HBsAg) and HBV DNA by 6 months post-treatment. In non-human primates, CRMA-1001 induced transient liver transaminase elevations only at the highest dose tested. Expression and DNA methylation profiling revealed no detectable unintended targets in the human genome. These findings support the initiation of clinical development of CRMA-1001 as a finite treatment course with the potential for functional cure in individuals living with CHB.

sample_organism:
Homo sapiens
Mus musculus
Hepatitis B virus

overall_design: RNA-seq and Methylation-seq libraries for a multiple in-vitro and in-vivo studies assessing off-target specificity and on-target efficacy of CRMA-1001. Study includes samples treated with HBV targeting epigenetic silencer CRMA-1001 and associated controls.

first: Yesseinia

last: Anglero-Rodriguez

first: Qiang

last: Xiong

first: Sarah

last: Voytek

first: Glen

last: Acosta

first: Rayman

last: Choo-Wing

first: Lenka

last: Hoffman

first: Arogya

last: Khadka

first: Jhon

last: Medina

first: Caroline

last: Mugambwa

first: Chloe

last: Pantano

first: Sivan

last: Harel

first: Amber

last: DiPiazza

first: Sameer

last: Abraham

first: Erica

last: Hildebrand

first: Ricardo

last: Ramirez

first: Ava

last: Zhai

first: Xiaoyun

last: Guo

first: Sahar

last: Abubucker

first: Chih-Wei

last: Ko

first: Cristiana

last: Giancarlo

first: Bradley

last: Niesner

first: Martino

last: Alfredo Cappelluti

first: Matteo

last: Conti

first: Lorena

last: Donnici

first: Pietro

last: Spinelli

first: Taesun

last: Eom

first: Mary

last: Morrison

first: Ari

last: Friedland

first: Raffaele

last: De Francesco

first: Angelo

last: Lombardo

first: Vic

last: Myer

first: Aron

last: Jaffe

first: Melissa

last: Bonner

middle: L


title: Development of an Optimized Epigenetic Silencer to Transcriptionally Inactivate Viral DNA in Chronic Hepatitis B [NHPAmpliconBisulfiteseq]

first: Jennifer

last: Marlowe

first: Yesseinia

last: Anglero-Rodriguez

first: Qiang

last: Xiong

first: Sarah

last: Voytek

first: Glen

last: Acosta

first: Rayman

last: Choo-Wing

first: Lenka

last: Hoffman

first: Arogya

last: Khadka

first: Jhon

last: Medina

first: Caroline

last: Mugambwa

first: Chloe

last: Pantano

first: Sivan

last: Harel

first: Amber

last: DiPiazza

first: Sameer

last: Abraham

first: Erica

last: Hildebrand

first: Ricardo

last: Ramirez

first: Ava

last: Zhai

first: Xiaoyun

last: Guo


title: Development of an Optimized Epigenetic Silencer to Transcriptionally Inactivate Viral DNA in Chronic Hepatitis B [WholeGenomeMethylseq]

first: Jennifer

last: Marlowe

first: Yesseinia

last: Anglero-Rodriguez

first: Sahar

last: Abubucker

first: Chih-Wei

last: Ko

first: Cristiana

last: Giancarlo

first: Bradley

last: Niesner

first: Martino

last: Alfredo Cappelluti

first: Matteo

last: Conti

first: Lorena

last: Donnici

first: Pietro

last: Spinelli

first: Taesun

last: Eom

first: Mary

last: Morrison

first: Ari

last: Friedland

first: Raffaele

last: De Francesco

first: Angelo

last: Lombardo

first: Vic

last: Myer

first: Aron

last: Jaffe

first: Melissa

last: Bonner


title: Development of an Optimized Epigenetic Silencer to Transcriptionally Inactivate Viral DNA in Chronic Hepatitis B [RNAseq]

first: Jennifer

last: Marlowe

first: Yesseinia

last: Anglero-Rodriguez

first: Qiang

last: Xiong

first: Sarah

last: Voytek

first: Glen

last: Acosta

first: Rayman

last: Choo-Wing

first: Lenka

last: Hoffman

first: Arogya

last: Khadka

first: Jhon

last: Medina

first: Caroline

last: Mugambwa

first: Chloe

last: Pantano

first: Sivan

last: Harel

first: Amber

last: DiPiazza

first: Sameer

last: Abraham

first: Erica

last: Hildebrand

first: Ricardo

last: Ramirez

first: Ava

last: Zhai

first: Xiaoyun

last: Guo


title: Type I IFN Dynamics Orchestrate Protective ICAM1⁺ Neutrophil Heterogeneity as an Early Checkpoint for Survival in Lethal Viral Infection [day0 RNA-Seq]

city: Tokyo

first: Riho

last: Saito

address: 7-3-1 Hongo Bunkyo-ku

department: Graduate School of Pharmaceutical Sciences

country: Japan

institute: University of Tokyo

summary: The early host response influences outcomes following viral infection. Here, we leveraged variability in survival after intranasal vesicular stomatitis virus (VSV) challenge in genetically identical mice to retrospectively profile systemic immune responses associated with survival or lethality. Survival was strongly associated with a robust systemic type I interferon (IFN) surge within 24 hours of infection, and blockade of type I IFN signaling during this narrow early window markedly reduced survival, establishing early IFN induction as a key determinant of outcome. This protective IFN surge rapidly remodeled the systemic immune landscape, inducing a specialized ICAM1⁺ neutrophil subset, primed within the bone marrow and characterized by a pro-inflammatory signature and enhanced phagocytic activity. Importantly, neutrophil-specific deletion of ICAM1 significantly reduced survival following viral infection. Together, these findings identify an early type I IFN-dependent checkpoint that shapes protective ICAM1+ neutrophil heterogeneity and disease trajectories, with implications for prognostic strategies and host-directed therapies.

overall_design: RNA-seq profiling of blood circulaing CXCR2+ neutrophils from wildtype c57b6j mice before intranasal infection with VSV.

first: Hiroki

last: Sugishita

first: Yukiko

last: Gotoh

first: Tomohiko

last: Okazaki


title: Independent cell type-specific expression and distal regulation of the 9p21 locus cell cycle regulators: p14ARF, p16INK4A, p15INK4A, and ANRIL [RNA-seq]

city: Cambridge

first: Neva

last: Durand

address: 75 Ames St

institute: Broad Institute

summary: The 9p21 locus encodes tumor suppressors p16INK4A and p14ARF (both encoded by CDKN2A), p15INK4B (CDKN2B), and a long non-coding RNA, ANRIL (CDKN2B-AS1). The ~1 megabase locus is notable for a high density of single nucleotide polymorphisms (SNPs) associated with aging-related diseases and traits. Despite clear importance, our understanding of the the cell-type specific expression dynamics and cis-regulatory mechanisms of the 9p21 transcripts has been constrained by the complexity of the transcript structures, low expression, and severe alterations to the locus in cancer cell lines. Here, we innovated custom computational and molecular tools to overcome these technical challenges and fill critical knowledge gaps in our understanding of 9p21 locus architecture and regulation of the 9p21 transcripts. Across tissues, we found that p15INK4b is the predominant transcript. We deconvolved the expression of the CDKN2A transcripts, p16INK4A and p14ARF, revealing stark differences in the expression of these overlapping but functionally distinct transcripts across tissues and cell types. Comparative analysis in a model of fibroblast senescence revealed a striking switch from preferential p14ARF expression in cycling cells, to p16INK4A and p15INK4b as cells age and senescence. Perturbation of putative cis regulatory elements nominated a network of promoters and enhancers that regulate p16INK4A, p14ARF, and p15INK4b and ANRIL. The identified elements are accessible in vivo, and can be used to guide studies into variant interpretation. Our systematic characterization of 9p21 transcript isoforms, promoters, and distal elements across cell states, in vivo tissues and senescence offers new mechanistic insights and a framework for future studies of this vital but poorly understood locus.

overall_design: This study systematically profiles the 9p21 locus to dissect transcript expression, chromatin architecture, and regulatory element function across multiple experimental modalities. Dial-up scRNA-seq (Gray et al. and Chan et al.) captures per-cell transcript expression, including new experiments outside published datasets. Region Capture Micro-C (RCMC) maps 3D chromatin contacts at the locus. ChIP-seq for CTCF and H3K27ac identifies regulatory protein binding and active enhancer marks. A pooled CRISPRa screen with CROP-seq and single-cell RNA-seq tests candidate regulatory elements for effects on gene expression. Complementary total RNA-seq in WI-38 cells across senescence provides temporal expression dynamics. Reference and supporting files, including custom annotations and curated target region sets, facilitate reproducibility and interpretation.

first: Elena

last: Torlai Triglia

first: Tyler

last: Miller

first: Kyung Lock

last: Kim

first: Salva

last: Casani Galdon

first: Joshua

last: D’Antonio

first: Noam

last: Shoresh

first: Kristin

last: Ardlie

first: David

last: Hendrickson

first: J Graham

last: Ruby

first: Bradley

last: Bernstein

first: Elizabeth

last: Gaskell


title: Transcriptomic profiling in estrogen receptor-positive breast cancer cell lines CAMA-1 and ZR-75-1 following CDK4/6 inhibitor treatment

city: Melbourne

first: Shom

last: Goel

address: 305 Grattan St

institute: Peter MacCallum Cancer Centre

summary: The retinoblastoma protein (Rb) is a tumour suppressor best known for repressing E2F transcription factors and halting cell cycle progression. In hormone receptor-positive (HR+) breast cancer, CDK4/6 inhibitors activate Rb by preventing its phosphorylation, forming a key component of current endocrine therapy regimens. How pharmacologically activated Rb remodels chromatin and influences transcription beyond cell cycle arrest remains poorly understood. Here we show that CDK4/6 inhibition induces redistribution of hypo-phosphorylated Rb to promoters and enhancers. While Rb predictably binds to cell cycle gene promoters to repress transcription, at other sites it unexpectedly promotes expression of oestrogen-responsive genes by integrating into oestrogen receptor (ER)-rich transcriptional hubs. CDK4/6 inhibition enhances ER target gene expression in breast cancer cells, patient-derived xenografts, and clinical HR+ breast cancer samples in an Rb-dependent manner. This reprogramming is mediated in part by KDM5A, whose interaction with Rb contributes to gene regulation at these loci. Critically, components of this Rb-driven ER transcriptional program are pro-proliferative. In endocrine-sensitive tumours, this can be neutralised with anti-oestrogen therapy, explaining therapeutic synergy. In endocrine-resistant settings such as ESR1-mutant breast cancer, the program persists, limiting therapeutic efficacy. These findings reframe Rb as a dual-function transcriptional regulator that, while enforcing cell cycle arrest, can also activate programs that counteract its tumour suppressor function.

overall_design: 3'RNA-seq profiling of estrogen receptor-positive cell lines ZR-75-1 and CAMA-1 treated with DMSO control, abemaciclib, or palbociclib. Three replicates per group.


title: A Functional Genomics-pharmacotranscriptomics Framework Identifies Host-directed Anti-influenza Agents

city: Beijing

first: Jianfa

last: Qiu

address: No. 16, Tianrong Street, Daxing District

department: Institute of Pathogen Biology

institute: Chinese Academy of Medical Sciences

summary: Influenza A virus (IAV) is a pervasive pathogen of humans, poultry, and livestock, posing an ongoing threat to global health and economic stability. The effectiveness of available antiviral drugs is increasingly compromised by the rapid evolution of drug-resistant IAV strains, highlighting the urgent need for new therapeutic strategies. Here, we present an integrative host-directed drug discovery framework that combines functional genomics and pharmacotranscriptomics to systematically identify compounds with anti-IAV potential. We first aggregated published genome-wide screens to assign each host gene a quantitative functional score reflecting its role in promoting or restricting IAV replication. These scores were then paired with gene expression profiles to estimate the overall antiviral status of host cells. Using large-scale pharmacotranscriptomic data, we screened nearly 20,000 drug-induced transcriptional signatures to identify compounds that shift host gene expression toward an antiviral state. Of 27 top candidates selected for validation, two compounds, lithocholic acid and ALW-II-49-7, not only inhibited IAV replication in vitro but also protected mice from lethal infection in vivo. By shifting the focus from viral to host targets, our approach offers a systematic and scalable path to discover antivirals that are less vulnerable to resistance and may be generalizable to other rapidly mutating pathogens.

overall_design: RNA-Seq profiling of lung tissue from C57BL/6 mice 24 hours after received lithocholic acid or ALW-II-49-7 treatment


title: FAP-derived CCL2 is required for adequate monocyte/macrophage infiltration to support acute skeletal muscle injury repair

city: New York

first: Gregory

middle: Robert

last: Smith

address: 1 Gustave L. Levy Pl

department: Neurology

institute: Mount Sinai Hospital

summary: Repair of acutely injured skeletal muscle relies on an adequate inflammatory response predominated by monocyte/macrophage infiltration. The process requires injured muscles to produce C-C chemokine ligand 2 (CCL2). The present study identified fibro/adipogenic progenitors (FAPs) as the primary source of CCL2 in acutely injured muscle where the pro-inflammatory subcluster of FAPs expanded rapidly and expressed the highest level of CCL2. FAP-specific deletion of Ccl2 largely abolished CCL2 production by acutely injured muscle, reducing monocyte/macrophage infiltration and impairing muscle regeneration. In vitro, the CCL2 expression by both mouse and human FAPs were induced by danger signal-containing muscle homogenates through toll-like receptor signaling. The CCL2 expression by mouse FAPs was also induced by infiltrating neutrophils partly through their secretion of pro-inflammatory cytokines. Our findings suggest an important immune sentinel role for FAPs, as they sense muscle damage, produce CCL2 to recruit inflammatory MOs, and promote injury repair.progression of dystrophic muscle in Duchenne muscular dystrophy (DMD) patients and DMD mouse model mdx5cv mice. The cellular and molecular mechanism underlying this difference has yet to be fully elucidated. To this end, the present study compared the single-cell transcriptomes of intramuscular monocytes/macrophages from uninjured and acutely injured quadriceps of 14 weeks-old wild-typed (WT) mice, and from quadriceps and diaphragm of age-matched mdx5cv mice, using single cell-based RNA sequencing (scRNA-seq) analysis. Our results identified multiple functionally diverse monocyte/macrophage clusters co-existing in each injured muscle sample. Both Ly6Chi and Ly6Clo intramuscular monocytes/macrophages were heterogenous, containing different clusters among different injury conditions. These clusters did not conform to strict M1/M2 activation, and were involved differentially in inflammation, extracellular matrix (ECM) remodeling, and myogenesis during skeletal muscle injury repair. These findings uncovered the heterogeneity of monocyte/macrophage activation in both acutely injured and dystrophic skeletal muscle, shedding light on the molecular and cellular mechanisms underlying the differential roles of monocytes/macrophages in acute skeletal muscle injury and muscular dystrophy in DMD.

overall_design: Single cell suspensions were prepared from C57 BL/6J wild-type mice 2 and 9 hours post BaCl2-induced acute skeletal muscle injury, and were then used for single cell-based RNA sequencing.

first: Xingyu

last: Wang

first: Yinhang

first: Ruoxi

last: Yuan

first: Frederique

last: Ruf-Zamojski

first: Sachiko

middle: T

last: Homma

first: Stuart

last: Sealfon

first: Lan

last: Zhou


title: Transcriptomic profiling in estrogen-receptor positive cell line MCF7 following treatment with abemaciclib and fulvestrant

overall_design: 3'RNA-seq profiling of estrogen receptor-positive cell line MCF7 treated with DMSO control, abemaciclib 500 nM, fulvestrant 5nM or combination (abemaciclib and fulvestrant) for 5 days. Three replicates per group.


title: CDK4 maintains cytoskeletal homeostasis by restraining actomyosin contractility

city: Lausanne

first: Giovanna

last: Ambrosini

address: Station 19

country: Switzerland

institute: EPFL

summary: Cyclin-dependent kinase 4 (CDK4) is best known for its canonical role in cell-cycle control, yet how CDK4 activity intersects with cellular architecture remains poorly defined. Here, we uncover a non-canonical function of CDK4 in maintaining cytoskeletal mechanical homeostasis in triple-negative breast cancer (TNBC) cells. We show that CDK4 phosphorylates the RhoA-targeting RhoGAP Myo9b at serine 1935, enhancing its GAP activity and restraining RhoA–ROCK–pMLC-dependent actomyosin contractility. Loss or inhibition of CDK4 alters cell morphology, disrupts actin organization, and increases contractility. Elevated contractility in CDK4-deficient cells induces collapse of the intermediate filament network, characterized by Vimentin reorganization and mitochondrial redistribution, indicating a higher-order defect in cytoskeletal architecture. Furthermore, CDK4 expression negatively correlates with pMLC levels in both mouse TNBC tumors and human breast cancer samples, supporting the physiological relevance of this pathway. Together, these findings identify CDK4 as a regulator of cellular mechanical stability, integrating actin dynamics, intermediate filament integrity, and organelle positioning, and reveal an unexpected role for CDK4 beyond cell-cycle regulation.

overall_design: RNA samples coming from tumors of  CDK4WT and CDK4KO MDA-MB-231 injected cells in nude mice

first: Kanishka

last: Parashar

first: Sarah

last: Geller

first: Arianna

last: Ravera

first: Catherine

last: Roger

first: Barney

last: F. Drake

first: Jialin

last: Shi

first: Silvia

last: Prieto Baños

first: Sévan

last: Stroh

last: Moi

first: Laia

last: Simo Riudalbas

first: Christophe

last: Dessimoz

first: Georg

last: E. Fantner

first: Dirk

last: Fasshauer

first: Dorian

last: V. Ziegler

first: Lluis

last: Fajas


title: Development of an Optimized Epigenetic Silencer to Transcriptionally Inactivate Viral DNA in Chronic Hepatitis B

first: Jennifer

last: Marlowe

sample_organism:
Macaca fascicularis
Homo sapiens
Mus musculus
Hepatitis B virus

overall_design: Refer to individual Series

first: Yesseinia

last: Anglero-Rodriguez

first: Qiang

last: Xiong

last: Voytek

first: Glen

last: Acosta

first: Rayman

last: Choo-Wing

first: Lenka

last: Hoffman

first: Arogya

last: Khadka

first: Jhon

last: Medina

first: Caroline

last: Mugambwa

first: Chloe

last: Pantano

first: Sivan

last: Harel

first: Amber

last: DiPiazza

first: Sameer

last: Abraham

first: Erica

last: Hildebrand

first: Ricardo

last: Ramirez

first: Ava

last: Zhai

first: Xiaoyun

last: Guo

first: Sahar

last: Abubucker

first: Chih-Wei

last: Ko

first: Cristiana

last: Giancarlo

first: Bradley

last: Niesner

first: Martino

last: Alfredo Cappelluti

first: Matteo

last: Conti

first: Lorena

last: Donnici

first: Pietro

last: Spinelli

first: Taesun

last: Eom

first: Mary

last: Morrison

first: Ari

last: Friedland

first: Raffaele

last: De Francesco

first: Angelo

last: Lombardo

first: Vic

last: Myer

first: Aron

last: Jaffe

first: Melissa

last: Bonner


title: The novel hypomethylating agent NTX-301 reprograms epigenetic and Hippo signaling pathways and exhibits pre-clinical activity in venetoclax-resistant and TP53-mutant AML

city: houston

first: Suresh

last: Satpati

state: Texas

address: 1901 east road scrb4

department: GENOMIC MEDICINE

institute: MD ANDERSON CANCER CENTER

summary: Combinations of Hypomethylating agents (HMA) and BCL-2 inhibitor venetoclax (VEN) are frontline therapies for patients with acute myeloid leukemia (AML) with high response rates, but patients ultimately relapse, especially those with TP53 mutations. We investigated therapeutic efficacy and mechanisms of action of NTX-301, a next-generation HMA and demonstrate that NTX-301 is superior to 5-azacytidine (5-AZA), exhibits activities in 5-AZA or VEN-resistant AML and synergizes with VEN in VEN or VEN/HMA resistant and TP53-mutant AML blasts and stem/progenitor cells both, in vitro and in vivo in PDX models. NTX-301 inhibits DNMT1 and increases p73, caspase-8, and activated caspase-8 in TP53-WT and TP53-mutant cells and activates p53 signaling. Methylation profiling analyses revealed that NTX-301 is a more selective hypomethylating agent compared to 5-AZA. Pathway analysis of 954 commonly hypomethylated genes showed profoundly greater enrichment of Hippo signaling in NTX-301-treated compared to 5-AZA-treated cells, and enrichment of insulin signaling, VEGF pathway, and cell cycle selectively in NTX-301- but not in 5-AZA-treated cells. NTX-301-mediated Hippo signaling was validated at protein levels. Data suggest that NTX-301 displays more potent anti-leukemia activities compared to 5-AZA and synergizes with VEN in VEN-resistant and TP53-mutant AML in part by suppressing DNMT1 and inducing DNA damage responses and extrinsic apoptosis and by inducing p53 and demethylating LATS1/2, thus activating Hippo signaling.

overall_design: Genome-wide methylation analysis: We applied Reduced Representation Bisulfite Sequencing (RRBS)33,34 to map methylated cytosines in TP53-WT, -KO, and -mutant (R175H and R248Q) Molm13 cells and in these cells treated with NTX-301 or 5-AZA (48 h). The genomic DNA was digested with MspI and We then implemented a comprehensive analysis to process RRBS data and identify differentially methylated regions (DMRs) between TP53-WT, -KO, and -mutant (R175H, R248Q) conditions or between cells treated with NTX-301 and 5-AZA. Initially, raw sequencing reads were preprocessed using fastp35. During this step, adapter sequences were removed, and low-quality bases were trimmed from the ends of reads. As a result, we retained approximately 95% of bases with a PHRED quality score >30. Next, high-quality reads were aligned to the human reference genome hg38 using BWA‐MEM36. The aligned reads were then processed using SAMtools37, where only properly paired reads were retained, and sorting was performed. In the further filtering step, the sorted reads were marked to avoid duplicate reads introduced by PCR amplification. Post-alignment, we utilized Bismark, a specialized tool for bisulfite sequencing data, to map methylation calls across the genome. Bismark performs both alignment and methylation extraction, accounting for the C-to-T conversions characteristic of bisulfite-treated DNA, thereby enabling accurate detection of methylation patterns at CpG sites. To identify biologically relevant DMRs, we employed the DMRseq R38 package. DMRseq is designed to detect contiguous methylation changes over regions and genomic blocks, rather than isolated CpG sites, allowing for more robust and functionally informative methylation profiling. The entire workflow, followed for all the samples and interpretation of methylation differences was carried out using the detected regions at a beta value range <-1 - >1.Illumina-compatible cytosine-methylated adaptors were ligated to the enzyme-digested DNA. Following repair, size-selected fragments representing sequences from 40-bp to 200-bp were bisulfite-converted and final library preparation was done by PCR amplification. After purification with magnetic beads, the libraries were pooled and subsequently sequenced in an Illumina sequencing next-generation instrument. Random bases adjacent to barcode sequences allow for unique molecule identification and removal of PCR duplicates during data analysis.

first: Bing

last: Carter

first: Po Yee

last: Mak

first: Edward

last: Ayoub

first: Steffen

last: Boettcher

first: Lauren

last: Ostermann

first: Yue

last: Wei

first: Guillermo

last: Garcia-Manero

first: Torsten

last: Haferlach

first: Kunal

last: Rai

first: Michael

last: Andreeff


title: Rb CUT&RUN profiling in ovarian cancer cell lines following CDK2 inhibitor treatment

first: Shom

last: Goel

overall_design: CUT&RUN for Rb in high grade serous ovarian cancer cell lines OVCAR-3 and Kuramochi treated with DMSO control or the CDK2 inhibitor INX-315 300 nM for 2 days. Two replicates per group.


title: BCL-2 Inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques

city: Atlanta

first: Gregory

middle: K

last: Tharp

state: GA

address: 954 Gatewood Dr

department: Developmental and Cognitive Neuroscience

institute: Yerkes National Primate Research Center

summary: The anti-apoptotic molecule BCL-2 favors the maintenance of the CD4+ T-cell reservoir during Human immunodeficiency virus (HIV) infection. We investigated directly in-vivo whether BCL-2 inhibition using venetoclax at the initiation of antiretroviral therapy (ART) would reduce the size of the viral reservoir. Twenty-four SIVmac239-infected rhesus macaques (RMs) were initiated on ART at day 14 post-infection (p.i.), alone or in combination with either 10-day treatment with venetoclax or venetoclax plus CD8α depletion, and followed up to day 294 p.i. A rapid, statistically significant, and sustained reduction in the intact SIV reservoir was observed in venetoclax-treated RMs in blood and lymph nodes (LNs). This reduction was driven by reduced survival and depletion of CD4+ T-cell subsets that critically contribute to the reservoir. CD4+ T-cells that persisted after venetoclax treatment exhibited elevated per-cell levels of BCL-2, reduced expression of pro-apoptotic molecules such as PUMA, increased expression of additional anti-apoptotic molecules, including BCL-xL, and a partial reduction in apoptotic sensitivity in ex vivo assays. These findings provide mechanistic insights for the venetoclax-induced pro-cell death changes in CD4+ T-cells, support the rationale for extended venetoclax dosing, and suggest that combining BCL-2 inhibition with agents targeting additional anti-apoptotic molecules can enhance clearance of the viral reservoir in HIV cure strategies.

overall_design: Total CD4+ T-cells  isolated from PBMCs from 12 SIV infected ART (antiretroviral therapy) treated Rhesus Macaques in three treatment groups (control=4,Venetoclax=4,Venetoclax+Anti-CD8a=4) at two timepoints were profiled for RNA-Seq expression

first: Tomas Raul Wiche

last: Salinas

first: Justin

last: Harper

first: Claire

last: Deleage

first: Kevin

last: Nguyen

first: James

last: Auger

first: Hannah

last: Flores

first: Amelia

last: Wilkes

first: Rachelle

last: Stammen

first: Jennifer

last: Wood

first: Steven

last: Bosinger

first: Mackenzie

last: Cottrell

first: Jeffrey

last: Lifson

last: Laird

first: Brandon

middle: F

last: Keele

first: R Brad

last: Jones

first: Andrew

last: Badley

first: Guido

last: Silvestri

first: Deanna

last: Kulpa

first: Mirko

last: Paiardini


title: Methyglyoxal reshapes the transcriptional network of human retinal endothelial cells [RNA-seq]

status: Public on Jun 30 2026

city: Naples

first: Valerio

last: Costa

state: Italy

address: Via P. Castellino, 111

department: Institute of Genetics and Biophysics

institute: National Research Council

summary: Diabetic retinopathy (DR) is a complex microvascular complication of diabetes and a leading cause of vision impairment. A primary event of DR is the functional impairment of microvascular cells (i.e., pericytes and endothelial cells) and pathological changes in the retinal neurovascular unit. In diabetes-related complications, advanced glycation end products (AGEs) play a pivotal role in oxidative damage induced by chronic hyperglycemia particularly in damaging retinal endothelial cells. Methylglyoxal (MGO) is the most reactive AGE precursor, able to induce vascular damage, neuroretinal dysfunction and retinal lesions. Here, we demonstrate that sublethal doses of MGO induce protein glycation adduct formation in human retinal endothelial cells (hRECs), impairing the migratory and tube-forming capabilities. Moreover, transcriptome and miRNome analyses highlighted extensive perturbations in gene expression and microRNA profiles, especially related to gene expression regulation, cell cycle, cell death and vasculature development.

overall_design: To assess, at the molecul level, the pathological changes in the retinal neurovascular unit caused by methylglyoxal (MGO), we expsoed primary human retinal endothelial cells (hRECs) to a fixed sublethal dose of MGO. Then, we analyzed the gene expression changes by transcriptome analysis (bulk RNA-Sequencing) and miRNome analyses.

first: Alfredo

last: Ciccodicola

first: Marianna

last: Aprile

first: Claudia

last: Miele

first: Cecilia

last: Nigro


title: The CLOCK/BMAL1 protein interaction landscape at the chromatin reveals homeodomain transcription factors as modulators of tissue-specific circadian transcription

city: Martinsried

first: Tobias

last: Straub

address: Großhadener Str. 9

department: Biomedical Center, Bioinformatics

country: Germany

institute: LMU Munich

summary: Although the molecular mechanism of the circadian clock is conserved across cells, its transcriptional outputs are highly tissue specific. To experimentally explore how the core CLOCK/BMAL1 heterodimer achieves this specificity, we investigated its protein interaction landscape at the chromatin by employing a method that combines chromatin immunoprecipitation with mass spectrometry-based quantitative proteomics (ChIP–MS). This approach yielded the first two-dimensional (temporal and tissue-specific) interaction map of CLOCK/BMAL1 at the chromatin and revealed a complex organ-dependent landscape of clock-associated protein interactions. Among these we identified three homeodomain containing transcription factors -PROX1, HFN1B and HOXA5- in liver, kidney and lung, respectively. Functional analyses demonstrated that these factors colocalize with CLOCK/BMAL1 at the chromatin physically interacting via their homeodomain and the BMAL1 C-terminal transactivation domain and act as transcriptional repressors. Deletion of these homeodomain factors in organ-derived cell lines led to upregulation of core clock genes and disrupted rhythmic transcription of tissue-specific targets. Our findings uncover a new class of tissue-specific circadian transcriptional repressors and suggest that the molecular clock does not solely impose a universal temporal program but is instead modulated by chromatin-bound cofactors—such as PROX1, HNF1B, and HOXA5—that shape tissue-specific transcriptional outputs

overall_design: BMAL1 and PROX1 ChIP-seq of the liver from C57BL/6 mice collected at ZT7. BMAL1 and HNF1B ChIP-seq of the kidney from  C57BL/6 mice collected at ZT8

first: Fatih

last: Aygenli

first: Lukas A.

last: Huschet

first: Andrea

last: Ribeiro

first: Darina

last: Barkhatova

first: Celine

last: Jouffe

first: Riccardo

last: Trozzo

first: Jerome S.

last: Menet

first: Roland

last: Rad

first: Kenneth

last: Dyar

first: Maciej

last: Lech

first: Alicia

last: Michael

first: Maria S.

last: Robles


title: Age-associated changes in gene expression in mouse lung

first: Keiko

last: Akasaka-Manya

address: 35-2 Sakae-cho

institute: Tokyo Metropolitan Institute of Gerontology

summary: This study investigates age-associated changes in N-glycosylation across mouse organs. As part of this analysis, gene expression profiling by bulk RNA-seq was performed on lung tissues from mice at different ages to characterize age-related transcriptional changes.

overall_design: Bulk RNA-seq analysis of lung tissues from C57BL/6NCr mice at 6, 12, 20, and 30 months of age to identify age-associated transcriptional changes.

first: Hiroshi

last: Manya


title: Transcriptomic profiling in ZR-75-1 parent and RB1 knockout cells following treatment with abemaciclib

first: Shom

last: Goel

overall_design: RNA-seq profiling in estrogen receptor-positive cell line ZR-75-1 parental cells and isogenic RB1 knockout cells, treated with DMSO control or abemaciclib 500 nM for 4 days. Three replicates per group.


title: Rb CUT&RUN profiling in estrogen receptor-positive breast cancer cell line MCF7 following palbociclib treatment

overall_design: CUT&RUN for Rb in estrogen receptor-positive cell line MCF7 parental cells treated with DMSO control or palbociclib 500 nM for 2 days. Two biological replicates per treatment group.


title: Modelling mental disorders in zebrafish. Neurexins severely modulate anxiety, social behaviors and aggression

city: Nathan

first: Oak

last: Hatzimanolis

state: QLD

address: 46 Don Young Rd

department: IBG

institute: Griffith University

summary: We generated a comprehensive collection of zebrafish neurexin knockout lines covering all family members, including alleles with transmembrane domain disruptions and deletions covering full genomic locus and partial gene region. All homozygous mutants were viable and showed no gross developmental abnormalities, enabling molecular profiling despite later‑onset behavioural phenotypes. This resource includes defined nrxn1a-nrxn1b, nrxn2a-nrxn2b, and nrxn3a-nrxn3b double gene mutant lines and provides a vertebrate model to investigate paralog‑specific consequences of neurexin loss of function. The RNA‑seq FASTQ files deposited in this GEO submission were generated from these neurexin mutant and matched control zebrafish and support analysis of transcriptional changes associated with neurexin deficiency.

overall_design: Poly (A) selected bulk RNA‑seq was performed on whole‑brain tissue from adult zebrafish neurexin mutant lines. The dataset includes neurexin 1 full‑loci (nrxn1a_full-nrxn1b_full), partial (nrxn1a_part-nrxn1b_part), and transmembrane (nrxn1a_tmr-nrxn1b_tmr) deletions; neurexin 2 full‑loci (nrxn2a_full-nrxn2b_full) and transmembrane (nrxn2a_tmr-nrxn2b_tmr) deletions; and neurexin 3 full‑loci (nrxn3a_full-nrxn3b_full) and transmembrane (nrxn3a_tmr-nrxn3b_tmr) deletions. Wild‑type zebrafish were used as controls. Three independent biological replicates were sequenced for each genotype.

first: Quynh

last: Nguyen

first: Fangfei

last: Guo

first: Joyosmita

last: Das

first: Bryan

last: Mowry

first: Alexandre

last: Cristino

first: Jean

last: Giacomotto


title: Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements [END-seq]

city: Shanghai

first: Yu

last: Liang

address: Yueyang Road 320

institute: CEMCS, CAS

summary: While the resurrection of transposons is tightly linked with cancer, neurodegenerative disorder and other pathologies, the precise suppression mechanisms and mobilization events of transposons during somatic development remain largely obscure. Here, we present a highly conserved mechanism that prevents transposon activation and mobilization. By tracking transposition events, we identified that Cramp1 plays a pivotal role in safeguarding both Drosophila and mouse development through silencing transposon mobility. Cramp1 was characterized as a major factor that specifically binds to the DNA sequences of histone gene cluster through its SANT domain, thereby initiating his1 transcription. The linker protein H1 then physically interacts and recruits Nsd to catalyze H3K36 dimethylation, which subsequently promotes proper deposition of both H4K20m3 and H3K9me3 to H3K36me2 established heterochromatin region for transposon silencing. In the absence of Cramp1 protection, uncontrolled transposons will induce massive DNA breaks, leading to abnormal hindgut regeneration in Drosophila and disrupted embryonic erythropoiesis in mice. Our finding highlights the endless arms race between hosts and transposons happening during evolution, wherein the key factors also evolve to suppress transposon mobilizations during somatic development.

overall_design: We employed Nanopore sequencing to capture the bona fide mobilization events within Drosophila hindguts and RNA-seq and scRNA-seq to quantify transposon expression. Combined with END-seq and ChIP-seq, we were able to gain a comprehensive understanding of the breakpoints generated at transposon insertion sites and the changes in histone modifications on the transposons.

first: Yini

last: Luo

first: Shuheng

last: Wu

first: Yazi

last: Deng

first: Wei

first: ZZ

last: Zhang

first: Lu

last: Wang


title: KRT6A enhances radiotherapy resistance in lung squamous cell carcinoma via activation of the autophagy pathway through RAB39B [RNA-Seq 2]

city: Dalian

first: Dachuan

last: Shen

address: No. 10, Xuefu Street, Dalian Economic and Technological Development Zone

institute: Dalian University

summary: Abstract  Background: Radiotherapy is the cornerstone for lung squamous cell carcinoma (LUSC) treatment, yet its efficacy is often limited by the development of radioresistance. Understanding the molecular mechanisms driving this resistance is critical for improving therapeutic outcomes. Results: In this study, we established a radioresistant LUSC cell line and identified KRT6A as a pivotal gene involved in radiotherapy resistance. Transcriptome sequencing and further validation revealed RAB39B as a downstream target of KRT6A. The KRT6A-RAB39B axis promotes radioresistance by activating the autophagy pathway, enhancing cancer cell survival in response to radiation stress. Mechanistic studies confirmed that KRT6A regulates autophagy through modulation of RAB39B expression. Conclusions：This work is the first to uncover a role of the KRT6A-RAB39B axis in LUSC radioresistance, offering new insights into the mechanisms and potential targets underlying radiotherapy failure.

overall_design: Total RNA was extracted from SK-MES-1 and radiotherapy-resistant cell line SK-MES-1-RR cells and subjected to RNA-seq.

first: Zaishuang

last: Ju

first: Yutong

first: Zhiqi

last: Zheng

first: Eric

last: Lam

first: Ruoyu


title: Dietary Fat Source Programs Distinct Plasma MicroRNA Signatures with Divergent Metabolic and Cognitive Trajectories in a Primate Model

status: Public on Jun 27 2026

city: Saclay

first: Mohammed

last: TAOUIS

address: NeuroPSI

institute: CNRS

type: Non-coding RNA profiling by high throughput sequencing

summary: Dietary fat composition profoundly influences metabolic and cognitive health, yet the molecular mechanisms underlying these effects, particularly during critical developmental windows, remain incompletely understood. This study aimed to determine whether dairy fat-based diet versus vegetable fat-based diet induces distinct plasma miRNA signatures with divergent metabolic and neuroprotective consequences in both aged animals and developmentally programmed offspring.  Using the gray mouse lemur (Microcebus murinus), a non-human primate model of aging and neurodegeneration, aged females and offspring born to mothers fed isocaloric dairy fat-based (D) or vegetable fat-base (V) diets were studied. Plasma miRNA profiling was performed by small RNA sequencing. Four offspring groups (DD, DV, VD, VV) were examined to disentangle prenatal and postnatal dietary fat effects. Hepatic molecular validation was performed by Western blot and qPCR. In aged animals, dairy fat-based diet upregulated miR-132, miR-100, and miR-130a, described to be associated with insulin sensitivity and neuroprotection, while vegetable fat-based diet elevated miR-107, miR-146b, and let-7g, known as biomarkers of insulin resistance and neuroinflammation. Hepatic SOCS3 protein and pro-inflammatory cytokines were significantly elevated in vegetable fat-based diet fed animals, confirming insulin signaling impairment prior to detectable metabolic changes. In offspring, prenatal dairy fat-based diet created persistent miRNA signatures in adulthood independent of postnatal diet, upregulating let-7f, miR-301a, and miR-502a, while prenatal vegetable fat-based diet elevated miR-204 and miR-381, known to be associated with impaired insulin signaling and neurological development. Sustained dairy fat-based diet amplified protective effects through coordinated miR-132/let-7/miR-29b upregulation. These primate-derived miRNA signatures mirror human biomarkers of type 2 diabetes and Alzheimer's disease, establishing translational potential for early-life nutritional strategies targeting metabolic-cognitive health programming.

overall_design: Plasma microRNA profiling in microcebus murinus subjected to dairy or vegetable fat-based diets.

first: Marianne

last: Prevost

first: Yohann

last: Chaudron

first: Ghislaine

last: Poizat

first: Laure

last: Riffault

first: Corinne

last: Marmonier

first: Clemence

last: Penhoat

first: Bernadette

last: Delplanque

first: Yacir

last: Benomar

first: Fabien

last: Pifferi

last: Taouis


title: A Pseudomonas aeruginosa LysR-type transcriptional regulator, PA1290, essential for productive biofilm and influences virulence and pathogenesis

city: Honolulu

first: Hung

last: Vo

state: Hawaii

address: 1800 East-West Road Life Sciences Building, Rm 318

department: Microbiology

institute: University of Hawaii at Manoa

summary: The transposon insertion mutation of regulator PA1290 (PA1290∷Tn) significantly reduced biofilm formation, while enhancing virulence in Drosophila melanogaster fruit fly and BALB/C mouse infection models. This regulator influenced bacterial motility, c-di-GMP signaling, and the RhlI-RhlR and Pseudomonas quinolone signal (PQS) quorum-sensing (QS) systems. We used  RNA-seq assays to identify the regulatory mechanisms of PA1290. We observed that 391 genes were up-regulated and 114 genes were down-regulated in the absence of PA1290, many of which are involved in rhamnolipid synthesis, type II, type III, and type VI secretion systems, and QS systems.

overall_design: The mutant PA1290::Tn and the wt PA01 strain were grown overnight in LB broth, diluted 100-fold into fresh LB broth, and grown in the same biofilm growth condition (30oC, no shake, 48 hours), as described above. Bacteria were harvested, and total RNA was isolated using the Qiagen RNeasy Mini Kit (Qiagen), with on-column DNase I treatment; rRNA was depleted using RiboZero (Epicentre®); and Illumina® NGS libraries were created and sequenced at TUCF Genomics (http://tucf-genomics.tufts.edu/). All transcriptomic analyses were done in biological triplicate. The transcriptional profiles of the mutant PA1290∷Tn were compared with those of wt PA01 to identify the specific sets of genes that the regulator PA1290 controls. RNA-seq results were analyzed using software Rockhopper (https://cs.wellesley.edu/~btjaden/Rockhopper/), which was designed for analysis of bacterial RNA-seq data

first: Yun

last: Heacock-Kang

first: Jan

last: Zarzycki-Siek

first: Ian

last: A. McMillan

first: Tung

last: Hoang


title: Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells

city: San Antonio

first: Nu

last: Zhang

state: TX

address: 7703 Floyd Curl Drive

department: Department of MIMG

institute: UT Health San Antonio

summary: Memory T cells are critical for vaccines and T-cell-based therapies. However, the differentiation path of memory T cells is not completely understood. Early bulk cell population-based studies support a linear model, in which effector T cells lose the effector program and dedifferentiate into memory T cells. Recent research supports a bifurcation model, where T cells choose one of the two paths, either the effector or the memory path, at an early stage of T cell responses. Terminal effector T cells lose the capacity to become memory T cells. Here, we first demonstrate that the expression of granzyme A is largely distinct from that of granzyme B and marks terminal cytotoxic effector CD8+ T cells with reduced polyfunctionality. Using a granzyme A-fate mapping mouse line and an acute viral infection model, we discovered that early memory T cells are largely derived from cells lacking a history of granzyme A expression, supporting the bifurcation model. Progressively, granzyme A-expressing terminal effector T cells dedifferentiate into functional long-term memory T cells. At the late memory phase, memory T cells are a mixed population composed of cells with different differentiation paths (i.e., the linear and the bifurcated paths) that coordinate to provide balanced immune protection.

overall_design: Naïve tdTomato- P14 T cells were adoptively transferred into C57BL/6 recipient mice, followed by LCMV Armstrong infection. Day 36 post-infection, two subsets of donor P14 T cells (KLRG1-TdTomato+ and KLRG1-TdTomato-) were FACS sorted from pooled spleen and lymph nodes. Sorted cells were subjected to bulk RNA-seq analysis.

first: Chaoyu

last: Ma

first: Wei

last: Liao

first: Saranya

last: Srinivasan

first: Kenneth

last: Fan

first: Tyng-An

last: Zhou


title: A Pseudomonas aeruginosa LysR-type transcriptional regulator, PA1290, essential for productive biofilm and influences virulence and pathogenesis [RNA-seq]


title: Development of an Optimized Epigenetic Silencer to Transcriptionally Inactivate Viral DNA in Chronic Hepatitis B [HybridCaptureMethylseq]

city: Boston

first: Jennifer

last: Marlowe

address: 201 Brookline Avenue

institute: nChroma Bio

summary: Approved chronic hepatitis B (CHB) therapies rarely result in functional cure, as they fail to permanently silence all transcriptionally active hepatitis B virus (HBV) DNA. CRMA-1001 employs an optimized epigenetic silencer that represses viral transcription through targeted deposition of DNA methylation on episomal and integrated HBV DNAs. In HBV mouse models, a single dose of CRMA-1001 produced >3 log10 reductions in viral biomarkers, which correlated with de novo methylation of HBV DNA. Three doses resulted in up to 90% of animals with undetectable hepatitis B surface antigen (HBsAg) and HBV DNA by 6 months post-treatment. In non-human primates, CRMA-1001 induced transient liver transaminase elevations only at the highest dose tested. Expression and DNA methylation profiling revealed no detectable unintended targets in the human genome. These findings support the initiation of clinical development of CRMA-1001 as a finite treatment course with the potential for functional cure in individuals living with CHB.

overall_design: RNA-seq and Methylation-seq libraries for a multiple in-vitro and in-vivo studies assessing off-target specificity and on-target efficacy of CRMA-1001. Study includes samples treated with HBV targeting epigenetic silencer CRMA-1001 and associated controls.

first: Yesseinia

last: Anglero-Rodriguez

first: Qiang

last: Xiong

first: Sarah

middle: B

last: Voytek

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last: Acosta

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last: Choo-Wing

first: Lenka

last: Hoffman

first: Arogya

last: Khadka

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last: Hildebrand

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middle: N

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last: Eom

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last: Morrison

first: Ari

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last: De Francesco

first: Angelo

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title: bulk RNAseq of Ccd18-Co cell line treated with cytokines

first: Simon

last: Koplev

address: Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, Puddicombe Way

department: Cambridge Stem Cell Institute

institute: University of Cambridge

overall_design: Ccd18-Co cell line unstimulated or stimulated with cytokines. N=4 replicates per treatment group.

first: Matthias

last: Friedrich