title: Diet-induced phospholipid remodeling dictates ferroptosis sensitivity and tumorigenesis in the pancreas

city: New Haven

first: Mandar

middle: Deepak

last: Muzumdar

state: CT

address: 333 Cedar Street

department: Genetics

institute: Yale University

summary: High-fat diet (HFD) intake has been linked to an increased risk of pancreatic ductal adenocarcinoma (PDAC), a lethal and therapy-resistant cancer. However, whether and how specific dietary fats drive cancer development remains unresolved. Leveraging an oncogenic Kras-driven mouse model that closely mimics human PDAC progression, we screened a dozen isocaloric HFDs differing solely in fat source and representing the diversity of human fat consumption. Unexpectedly, diets rich in oleic acid - a monounsaturated fatty acid (MUFA) typically associated with good health - markedly enhanced tumorigenesis. Conversely, diets high in polyunsaturated fatty acids (PUFAs) suppressed tumor progression. Relative dietary fatty acid saturation levels (PUFA/MUFA) governed pancreatic membrane phospholipid composition, lipid peroxidation, and ferroptosis sensitivity in mice, concordant with circulating PUFA/MUFA levels being linked to altered PDAC risk in humans. These findings directly implicate dietary unsaturated fatty acids in controlling ferroptosis susceptibility and tumorigenesis, supporting potential "precision nutrition" strategies for PDAC prevention.

overall_design: RNA-seq profiling of pancreata isolated from KrasLSL-G12D/+; Pdx1-Cre (KC) and (KrasLSL-G12D/+;Pdx-Cre;Leptinob/ob (KCO) mice fed a high-fat diet (HFD). KC mice  were fed an HFD for either 12 weeks or 3 weeks beginning at 6 weeks of age. KCO mice  were fed an HFD for 8 weeks beginning at 6 weeks of age. All mice were maintained on ad libitum high-fat diet.

first: Christian

middle: R

last: Ruiz

middle: D


title: PI-5-P links the Hippo Pathway and PI5P4K signaling [PIP4K2A/B shRNA]

status: Public on Apr 09 2026

city: La Jolla

first: Brooke

middle: M.

last: Emerling

state: CA

address: 10901 North Torrey Pines Road

department: Cell and Molecular Biology of Cancer Program

country: USA

institute: Sanford Burnham Prebys Medical Discovery Institute

type: Expression profiling by high throughput sequencing

summary: The phosphoinositide PI-5-P is a signaling lipid that mediates cellular responses to oxidative stress and DNA damage, however it is unclear how PI-5-P participates in these processes. Intracellular pools of PI-5-P are regulated by PI5P-Kinases (PI5P4Ks), but how PI5P4K activity is controlled has also remained elusive. Here, we used an unbiased screen to discover the core Hippo pathway kinases MST1/2 phosphorylate and inhibit PI5P4K signaling in vitro and in cells. We further show PI5P4Ks regulate several Hippo/YAP-related phenotypes in human cells, such as the interaction between the key Hippo proteins MOB1-LATS, and the genetic program governing epithelial-to-mesenchymal transition. Mechanistically, we show that MOB1 binds PI-5-P with high specificity and potency, providing a signaling connection between the Hippo Pathway and PI5P4Ks. These discoveries shed new light on how these two important evolutionary conserved signaling pathways are integrated to regulate metazoan development and human disease.

overall_design: Transcriptomics comparison of scrambled control shRNA versus PIP4K2A/B shRNA in HCC1806 cell line using RNA-seq

first: Lavinia

last: Palamiuc

first: Ryan

middle: M

last: Loughran


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

status: Public on Apr 10 2026

city: Xiamen

first: Huifen

last: Cao

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

state: Fujian

address: 668 Jimei Road

department: School of Biomedical Sciences

country: China

institute: Huaqiao University

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

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

first: Philipp

last: Kapranov


title: Divergent roles of SPOP and CHD1 in ACSL4 regulation reveal context-dependent vulnerabilities for targeting ferroptosis

city: Houston

first: Di

last: Zhao

state: Tx

address: Zayed Building Z7. 4018

institute: MD Anderson Cancer Center

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Genetic heterogeneity contributes to the variable therapeutic responses in prostate cancer (PCa). Frequent SPOP mutations and recurrent CHD1 deletions define distinct molecular subtypes of PCa with differential responses to anti-androgen therapy. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy. Here, we identify SPOP mutations and CHD1 deletion as key genetic determinants of ferroptosis susceptibility in PCa.

overall_design: ChIP-seq was performed in WT and SPOPW131G LNCaP cells using IgG control or CHD1 antibodies; SPOPW131G/CHD1KO LNCaP cells were treated with or without atorvastatin (10 𝜇M) for 48h, followed by ChIP-seq using IgG control or SP1 antibodies.

first: Feiyu

last: Chen

first: Qidong

last: Li

first: Yue

last: Lu

first: Boyi

last: Gan


title: Evolutionary transfer learning enables organism-wide inference of mammalian enhancer landscapes

city: Hanover

first: Chengxiang

last: Qiu

state: NH

address: Vail 604, 74 College St

department: Department of Molecular and Systems Biology

institute: Dartmouth College

summary: Understanding and modeling how a single human genome concurrently encodes gene regulatory programs for thousands of cell types remains a central challenge in genomics and machine learning. Most human cell types emerge during embryonic, fetal, and pediatric development which are inaccessible to comprehensive molecular profiling. To circumvent this, we hypothesized that the mismatch in evolutionary rates between cis-acting enhancers that modulate gene expression (fast) and the trans-acting regulatory factors that specify cell types (slow) creates an opportunity for 'evolutionary transfer learning'. Specifically, models trained to predict cell type-specific enhancers in one species should generalize to the orthologous cell types and enhancers of related species. To test this, we generated a single-cell atlas of chromatin accessibility spanning mouse embryonic day 10 (E10) to birth (P0). Using combinatorial indexing, we profiled 3.9 million nuclei from 36 staged embryos, resolving genome-wide accessibility in 36 cell classes and 140 cell types. We then trained a series of multi-output deep learning models (CREsted), each addressing limitations of the preceding approach, towards the goal of genome-wide prediction of distal enhancers across major developmental lineages. An 'evolution-naive' model achieved strong performance on heldout peaks, but exhibited two failure modes during genome-wide inference: overprediction at tandem repeats and conflation of promoter and distal enhancer grammars. An 'evolution-aware' model resolved these by regrouping accessible regions based on their retention and functional coherence across mammalian evolution, but failed to generalize across species. Finally, an 'evolution-augmented' model, STEAM (Synteny-aware Transfer learning for Enhancer Activity Modeling), incorporated enhancer orthologs from 241 mammalian genomes (Zoonomia) in a synteny-supervised manner. This increased the effective data scale by as much as 195-fold, markedly improving generalization across mammals despite greater label noise. We applied STEAM to the genome-wide inference of cell class-specific distal developmental enhancers in humans, mice (HumMus) and 239 additional mammals (BabaGanoush), i.e. 32 × 241 = 7,712 genome-wide distal enhancer prediction tracks. Together, our results unify advances in single-cell profiling, deep learning, and comparative genomics into a framework for the evolutionary transfer learning of noncoding regulatory grammars. More broadly, our work supports the view that model organisms and evolutionarily diverse genomes are indispensable resources for accelerating and enhancing the AI-enabled exploration of human biology.

overall_design: To profile chromatin accessibility across mouse embryogenesis, 36 frozen embryos were selected from a staged collection of 523 embryos spanning late gastrulation to birth (E8–P0), targeting one embryo per 6-hour interval from E10 to P0 (with the exception of E17.75). Female embryos were preferentially selected (29 female, 7 male) to minimize sex-related mapping artifacts. Whole frozen embryos — without tissue dissection — were processed using sci-ATAC-seq3 across six experiments grouped by gestational age range (E10–E13.75, E14–E15.75, E16–E18, E18.25–P0). Sequencing was performed on five Illumina NovaSeq runs, followed by demultiplexing, embryo assignment, trimming, alignment to mm10, and fragment profile generation.

first: Riza

last: Daza

first: Ian

last: Welsh

first: Rupali

last: Patwardhan

first: Beth

last: Martin

first: Tony

first: Shizhao

last: Yang

first: Niklas

last: Kempynck

first: Megan

last: Taylor

first: Olivia

last: Fulton

first: Truc-Mai

last: Le

first: Diana

last: O’Day

first: Jean-Benoît

last: Lalanne

first: Silvia

last: Domcke

first: Stephen

last: Murray

first: Stein

last: Aerts

first: Cole

last: Trapnell

first: Jay

last: Shendure


title: Bacterial extracellular vesicles from Streptococcus mutans drive OSCC progression through β-catenin signaling

city: Harbin

first: Yong

last: Fang

state: Hei longjiang

address: 157 Health Road, Nangang District, Harbin City

department: Department of Microbiology

institute: Harbin medical university

summary: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy in which microbial dysbiosis is increasingly recognized as a contributing factor, yet the pathogenic potential of bacterial extracellular vesicles (EVs) remains poorly defined. To determine whether Streptococcus mutans–derived EVs (SmEVs) influence OSCC progression, we isolated and characterized SmEVs from ATCC 35668 and examined their effects in CAL-27 cells and a nude-mouse xenograft model. SmEVs were readily internalized by OSCC cells and enhanced proliferative, migratory, and invasive capacities in vitro. Transcriptomic analysis revealed that SmEV exposure reshaped the CAL-27 gene expression landscape and prominently enriched the Wnt/β-catenin signaling pathway, accompanied by increased activation of β-catenin, TCF7, and FOSL1/Fra-1 in both cultured cells and xenograft tumors. DIA proteomics identified a broad array of SmEV proteins, and in silico docking highlighted several abundant, cancer-associated candidates with strong predicted interactions with β-catenin. In vivo, co-administration of SmEVs accelerated tumor growth and reinforced activation of the β-catenin axis. Collectively, these findings provide the first evidence that S. mutans–derived EVs promote OSCC progression through β-catenin–driven transcriptional programs and identify specific vesicular proteins as candidate mediators, offering new insights into microbe-derived factors as potential diagnostic or therapeutic targets in OSCC.

overall_design: We performed mRNA sequencing analysis on the oral cancer cell line CAL-27 with or without the action of Streptococcus mutans extracellular vesicles.

first: Guoding

last: Cao

first: Yichen

last: Jiang

first: Xinhang

last: Li

first: Ran

last: Liu

first: Kaili

first: Fikadu

last: Balcha

first: Mingyang

last: Ding

first: Meng

last: Yuan

first: Ting


title: Triggering mouth-resident antiviral CD8+ T cells potentiates experimental periodontitis

city: Cleveland

first: Michael

last: Stolley

state: Ohio

address: 9620 Carnegie Ave N Bldg

department: Department of Inflammation and Immunity

institute: Cleveland Clinic Lerner Research Institute

summary: Emerging evidence indicates that gingival-resident helper CD4+ T cells are major drivers of periodontal inflammation in response to commensal and pathogenic oral microorganisms. Whether tissue-resident memory CD8+ T cells (TRM), which principally safeguard against viruses and cancer but also drive certain autoimmune and inflammatory conditions, impact periodontitis progression and severity remain unknown. We asked whether local reactivation of oral CD8+ TRM of a defined antigen specificity could exacerbate ligature-induced periodontitis (LIP), a well-established model of periodontal disease in mice. Topical application of virus-mimicking peptides to the oral mucosa concurrent with LIP 1) intensified alveolar bone loss, 2) amplified gingival and cervical lymph node inflammation, and 3) stimulated gingival transcriptional changes in genes related to innate immune sensing and cell-mediated cytotoxicity. Therapeutic depletion of CD103-expressing oral CD8+ TRM in advance of LIP prevented exacerbation of disease. These observations provide evidence that oral CD103+ CD8+ TRM have the potential to participate in gingival inflammation, alveolar bone loss, and periodontitis.

overall_design: RNA-seq profiling of maxilla gingival tissue from mice subjected to ligature-induced periodontitis (LIP) with or without oral CD8+ TRM activation via topical virus-mimicking peptides applied to the oral mucosa, collected three and seven days post-LIP.

first: Flávia

last: M Saavedra

first: Danielle

last: Barbosa Brotto

first: Courtney

last: A Matson

first: Pavel

last: P Nesmiyanov

first: Mark

last: C Herzberg

first: Vaiva

last: Vezys

first: David

last: Masopust

first: J Michael


title: Spatial transcriptomics for intrathoracic adhesion in mice

city: Suita

first: Daisuke

last: Motooka

state: Osaka

address: 3-1, Yamadaoka

country: Japan

institute: NGS core facility, Research Institute for Microbial Diseases, Osaka University

summary: Intrathoracic adhesions (IAs) complicate thoracic surgery, causing risks such as bleeding, prolonged operative time, and postoperative air leakage. Severe adhesions (>10% pleura) often necessitate conversion from VATS to open thoracotomy due to dissection difficulties and pleural damage. Given the increasing role of lung segmentectomy and re-lobectomy for small or recurrent NSCLC, reoperations with IA are expected to rise, highlighting the need for effective IA prevention. This study aimed to establish such a murine IA model, evaluate pathological and gene expression changes, and identify targets to prevent lung–chest wall adhesions.

overall_design: B6 mice were anesthetized with ketamine, and intrathoracic adhesions were induced. On day 6 after adhesion induction, lung tissues were harvested, fixed in 4% formaldehyde, and embedded in paraffin blocks. Sections were cut at 5 µm intervals, and the samples were subsequently subjected to Visium spatial transcriptomic analysis.

first: Tomohisa

last: Sakaue

first: Yu

last: Mori

first: Hironori

last: Izutani


title: Strong Concordance of DNA Methylation Measures Between Venous and Capillary Blood - Implications for Human Epigenome Studies

city: Vancouver

middle: S.

last: Kobor

state: BC

address: 117-2194 Health Sciences Mall

department: Faculty of Medicine

country: Canada

institute: University of British Columbia

type: Genome binding/occupancy profiling by genome tiling array

summary: DNA methylation is tissue specific, which has profound implications for data analysis. While both capillary and venous blood samples are whole blood, they are not identical in their clinical profiles. Here we assess the congruency of DNA methylation from 20 individuals with matched venous and capillary blood draw DNA methylation.  We used DNA methylation profiles from Illumina EPIC v2 arrays assess the differences of these blood sources in quality control approches, in predicted immune cell proportions,  in DNA methylation based predictors including epigenetic clocks and lifestyle predictors, and performed an examplar EWAS

overall_design: Bisulphite converted DNA from 40 blood samples, either capillary or venous blood from 20 matched individuals, were hybridized to the Illumina Infinium HumanMethylationEPIC version 2.0 microarray to evaluate: i) Differences in DNA methylation profiles between venous and capillary blood draws, and ii) Differences in DNA methylation-data based predictors calculated from either venous or capillary blood. Thereafter an EWAS of age and sex was conducted.

first: Hannah-Ruth

last: Engelbrecht

first: Chaini

last: Konwar

first: Beryl

middle: C

last: Zhuang

first: Kristy

last: Dever

first: Julie

middle: L

last: MacIsaac

first: Tran

middle: K

last: Toan

first: Kim

last: Korinek

first: Zachary

last: Zimmer

middle: S


title: Transcriptome analyses of Arabidopsis natural accessions Col-0 and IP-Svi-0 at different tempearatures

city: Seoul

first: Zeeshan

last: Nasim

address: Anam-ro 145, Seongbuk-Gu

department: School of Life Sciences and Biotechnology

country: South Korea

institute: Korea University

summary: Plants are sessile organisms; thus they developed sophisticated endogenous mechanisms to detect and respond to various environmental cues . Our planet has diverse light and temperature conditions, to adopt in such a wide range of climatic conditions plants must have phenotypic plasticity. In addition to phenotypic plasticity plants also have variations in ontogenetic trajectory that results from genetic and epigenetic modifications leading to differential growth response to varying environment. To ensure successful adaptation and survivability in diverse climatic conditions a number of genetic polymorphisms are accumulated in various natural accessions of Arabidopsis. In this study, we investigated the reasons of photoperiod and temperature insensitive early flowering phenotype of San Vicente (IP-Svi-0) which was collected from San Vicente, Spain (Latitude: 43.39; Longitude: -7.39). Our RNA seq analysis showed decreased expression of MAF1-3 and 5

overall_design: To investigae differentially expressed genes in IP-Svi-0 natural accession and identifying imporant genes involved in its early flowering, we performed RNA sequencing of two different IP-Svi-0 and Col-0 seedlings at different temperatures.

first: Nasim

last: Zeeshan

first: Karim

last: Nouroz

first: Ahn

last: Ji-Hoon


title: Pulmonary fibroblast subsets demonstrate differentially enriched signaling pathways during fibrosis resolution and repair

city: Denver

first: Elizabeth

last: Redente

state: CO

address: 1400 Jackson Street

department: Pediatrics

institute: National Jewish Health

summary: The lungs have a remarkable capacity to undergo homoeostatic repair and regeneration after injury, which often occurs in patients with acute respiratory distress syndrome (ARDS) and in the single-dose bleomycin mouse model. Fibroblasts are critical mediators of fibrotic disease and RNA sequencing has identified significant heterogeneity within pulmonary fibroblast populations. However, the contribution of distinct fibroblast subsets to the repair process has been understudied compared to their role in fibrosis initiation and progression. Therefore, we sought to define the transcriptional landscape of three phenotypically-defined fibroblast subsets that occupy discrete spatial locations in naïve lungs. Using TdTomato-lineage tracing approaches, we identified and interrogated collagen1a1+ (Col1a1) fibroblasts, perilipin 2+ (Plin2) alveolar fibroblasts, and -smooth muscle actin+ (Acta2) myofibroblasts during fibrosis development and resolution after single-dose bleomycin. Quantification of fibroblast numbers showed that all three subsets expand during fibrosis and contract towards naïve levels with resolution. Principal component and gene-set enrichment analyses indicated that each subset undergoes major transcriptomic shifts during fibrosis development, converging on a similar pro-fibrotic transcriptional profile. However, during resolution, Plin2+ and Acta2+ fibroblasts revert towards a pre-fibrotic transcriptional state, whereas Col1a1+ fibroblasts acquire a distinct program that suggests suggesting an active role in mediating the repair processes.

overall_design: Bluk RNA-seq: Col1a1: Naïve (3 reps), 3wk bleo (3 reps), 8wk bleo (3 reps); Acta2: Naïve (3 reps), 3wk bleo (3 reps), 8wk bleo (3 reps); Plin2: Naïve (3 reps), 3wk bleo (3 reps), 8 wk bleo (2 reps)

first: Foster

last: Daniel G.

first: Javkhlan

last: Nomin

first: Black

last: Bart P.

first: Vestal

last: Brian E.

first: Riches

last: David W.H.

first: Redente

last: Eliabeth F.


title: The genetic basis for DNA methylation variation across tissue and development

city: Jerusalem

first: Batia

last: Azria

state: Israel

address: Jerusalem

country: Israel

institute: Hebrew university of Jerusalem

type: Methylation profiling by high throughput sequencing

summary: DNA methylation regulates gene expression and cell identity through development. By analyzing genome-wide methylation patterns in multiple tissues from genetically distinct mouse strains, we identify thousands of differentially methylated regions (DMRs) linked to sequence variants. These DMRs reveal key factor-binding regulatory motifs that govern methylation programming, with ubiquitous DMRs established early in embryogenesis, whereas cell-type-specific DMRs emerge later during tissue differentiation. Extending this approach to human data, we map over 21,000 methylation-associated SNPs, pinpointing genetic variants that regulate DNA methylation ubiquitously or in specific cell types. These findings highlight the role of transcription factor binding in shaping epigenetic landscapes and provide mechanistic insights to how genetic variation influences gene regulation and disease susceptibility. Our study establishes a systematic developmental framework for deciphering the genetic determinants of DNA methylation programming, offering a foundation for understanding epigenetics and phenotypic diversity with clinical implications in health and disease.

overall_design: DNA methylation profile  in multiple tissues from genetically distinct mouse strains

first: Jonathan

last: Rosenski

first: Ofra

last: Sabag

first: Howard

last: Marcus

first: Netanel

last: Loyfer

first: Yuval

last: Dor

last: Cedar

first: Tommy

last: Kaplan


title: Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency [ATAC-seq]

city: Yokohama

first: Tomohiko

last: Akiyama

state: Kanagawa

address: 3-9 Fuku-ura

department: School of medicine

institute: Yokohama city university

summary: The Y chromosome retains a limited number of protein-coding genes, yet their biological significance remains poorly understood. Here, we find UTY, a Y-linked homolog of the histone demethylase UTX, plays an essential regulator of pluripotency in human embryonic stem cells. Despite its low expression and weak enzymatic activity, UTY co-localizes with UTX at active cis-regulatory elements and contributes to the regulation of core pluripotency genes such as NODAL and LEFTY. Through genome-wide occupancy and transcriptome analyses of knockout cell lines, we show that UTY and UTX function redundantly to maintain proper localization of key transcription factors including OCT4 and SOX2. Dual loss of UTY and UTX leads to their mislocalization, widespread transcriptional dysregulation, and loss of pluripotency, without changes in H3K27 methylation. Instead, these effects are associated with changes in histone acetylation and altered chromatin accessibility, likely driven by recruitment of ATP-dependent chromatin remodelers, pointing to a non-enzymatic mechanism. Our findings uncover a novel role for UTY in stabilizing transcription factor binding and maintaining cell identity, demonstrating that even the evolutionarily compact Y chromosome retains critical regulatory functions in early human development.

overall_design: ATAC-seq to identify open chromatin regions in WT and UTX/UTY-KO hES cells


title: Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency [ChIP-seq]

overall_design: Chromatin immunoprecipitation DNA sequencing for H3K27ac and H3K27me3 in WT and UTX/UTY-KO hES cells


title: Loss of schizophrenia risk gene XPO7 disrupts neuronal excitability and network regularity via altered Na+ channel dynamics in human neurons

city: Cambridge

first: Lei

last: Cui

state: MA

address: 75 Ames st. room 8115b room 8115b

institute: Broad Institute of MIT and Harvard

summary: Schizophrenia is a highly heritable psychiatric disorder, yet the molecular mechanisms by which genetic risk contributes to disease pathophysiology remain largely unknown. In this study, we investigate the functional consequences of XPO7 loss of function (LoF) in human induced pluripotent stem cell (iPSC)-derived neurons, focusing on its role as a schizophrenia risk gene identified through recent large-scale exome sequencing analyses. By integrating high-precision electrophysiological measurements with transcriptomic, proteomic, and imaging approaches, we demonstrate that XPO7 LoF alters Na+ channel properties and availability, disrupts neuronal excitability, and impairs the synchrony and regularity of network activity. These functional deficits are accompanied by widespread molecular dysregulation affecting nucleocytoplasmic transport, ion channel function, and synaptic composition. Among the dysregulated proteins is Nav1.2, a voltage-gated sodium channel encoded by the schizophrenia-associated gene SCN2A, which exhibits aberrant subcellular distribution in XPO7 LoF neurons, characterized by increased somatic accumulation and reduced synaptic localization. Together, these findings position XPO7 as a critical regulator of neuronal excitability and connectivity, linking channelopathy to cellular phenotypes relevant to schizophrenia pathophysiology.

overall_design: RNA-seq on isogenic human iPSC-derived excitatory neurons carrying either heterozygous or homozygous XPO7 loss-of-function (LoF) mutations. Samples were collected at three stages of neuronal differentiation (Day 28, Day 42, and Day 56) to capture transcriptional changes across development. Parental (wildtype) iPSC-derived neurons were included as controls.

first: Jen

middle: Q

last: Pan


title: Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency [ChIP-seq_dualcross]

overall_design: Dual-crosslink chromatin immunoprecipitation DNA sequencing for transcription and chromatin related factors in WT and UTX/UTY-KO hES cells


title: Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency [RNA-seq]

overall_design: RNA-sequencing analysis for WT and UTX/UTY-KO hES cells


title: Estrogen Impacts NOD2-Dependent Regulation of Intestinal Homeostasis

city: Edmonton

first: Edan

last: Foley

state: Alberta

address: 116 st and 85 ave

department: Medical Microbiology and Immunology

institute: University of Alberta

summary: To investigate how NOD2 deficiency impacts gut homeostasis at the cellular level, prior to the onset of inflammation, we perform single-cell RNA sequencing on whole intestines from adult co-housed, in-crossed WT and nod2-/- siblings; minimizing impacts of environmental and genetic variability

overall_design: Five adult WT TL and five adult nod2-/- cohoused incrossed siblings with equal sex distribution were selected. Adult zebrafish intestines were dissected, dissociated into a single cell suspension, and processed for single-cell RNA sequencing.

first: Mckenna

last: Eklund


title: Single-cell and spatial transcriptomics in Phragmites australis reveal the association of B chromosomes with plant invasiveness

city: Helsinki

first: Cui

last: Wang

address: PL 65 (Viikinkaari 1)

country: Finland

institute: University of Helsinki

summary: Invasive plants can significantly disrupt native biodiversity, yet the genetic mechanisms driving their success remain poorly understood. This study investigates the genetic basis of invasiveness in the common reed (Phragmites australis), a resilient grass species that became invasive in North America following its introduction from Europe. By integrating whole-genome sequencing with bulk, single-cell, and spatial transcriptomics, we constructed a comprehensive single-cell atlas of the common reed's shoot system. UMAP analysis revealed 19 distinct cell clusters within the shoot, which were annotated using Gene Ontology (GO) enrichment to identify key cell types, including mesophyll, epidermal, bundle sheath, differentiating vascular cells, shoot apical meristems, and a cell cycle-associated cluster. We inferred key genes involved in the specification of several tissues, such as epidermal cells and ground meristems. For gene expression analysis, shoot tissues from three individuals of the invasive North American population and three from the native European population were included. Comparative transcriptomic analysis revealed significant upregulation of genes associated with the light-harvesting components of photosynthesis in several tissues of the invasive population, while genes involved in the respiratory burst related to defense responses were notably downregulated.

overall_design: Shoot tissue of one individual from the invasive population NAint61 was used for spatial transcriptomics to confirm the cell types.

first: James

last: Ord

first: Mengxiao

last: Yan

first: Yunfei

last: Cai

first: Hongjin

last: Shao

first: Lele

last: Lin

first: Jarkko

last: Salojärvi

last: Liu

first: Weihua

last: Guo


title: Functional redundancy between UTY and UTX in regulating the localization of transcription factors involved in pluripotency

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

overall_design: Refer to individual Series


title: m6a and NuRD complexes regulate monocytic differentiation and resistance to BCL2/BCL2L1 inhibitors in AML

city: Portland

first: Daniel

last: Bottomly

address: 3181 S.W. Sam Jackson Park Rd.

institute: Oregon Health and Science University

summary: Frontline use of the BCL2 inhibitor, venetoclax, for acute myeloid leukemia (AML) has resulted in broad improvements in patient outcome. A major remaining challenge is the development of venetoclax resistance, frequently driven by compensatory transcriptional programs that promote cell survival and differentiation. These changes reduce dependence on BCL2 in favor of alternative anti-apoptotic BCL2 family members such as MCL1 or BCL2L1 (BCL-XL). Using CRISPR-based genome-wide perturbation screens, we investigated the genetic dependencies of venetoclax and the BCL2/BCL2L1 dual inhibitor AZD4320. We identified the N6-methyladenosine (m6A) writer RBM15, and the Nucleosome Remodeling and Deacetylase (NuRD) complex interactor ZMYND8 as novel mediators of resistance to both venetoclax and AZD4320. Loss of RBM15 or ZMYND8 induced drug resistance, concurrent with alterations in BCL2 family expression and monocytic differentiation. Accordingly, in AML patient samples we found reduced expression of the respective m6a or NuRD complexes was significantly associated with monocytic differentiation and ex vivo resistance to the same drugs. These findings provide critical insights into previously undescribed mechanisms of BCL2 family inhibitor resistance in AML.

overall_design: Using a genome-wide CRISPR screen on OCI-AML2 cells, we performed comparisons of sgRNA read counts between DMSO and AZD4320 at Day 14.  Genes that were significantly depleted (enriched) relative to DMSO controls were deemed candidates for enhancing drug sensitivity (resistance).

first: Jackson

last: Brim-Edwards

first: Karen

last: Morris

first: Quinlan

last: Morrow

first: Stephen

last: Kurtz

first: Cristina

last: Tognon

first: Shannon

last: McWeeney

first: Tamilla

last: Nechiporuk

first: Kevin

last: Watanabe-Smith

first: Jeffrey

middle: W

last: Tyner


title: Genetic ablation of Pth4 disrupts calcium-phosphate balance, bone development, and kidney transcriptome in teleosts

city: Vigo

first: Luis

last: Méndez Martínez

address: Eduardo Cabello Nº6

country: Spain

institute: Instituto de Investigaciones Marinas (IIM-CSIC)

summary: Parathyroid hormone 4 (Pth4) is an evolutionarily conserved member of the PTH family, expressed in hypothalamic neurons and lost in eutherian mammals. In order to elucidate its role in mineral homeostasis and skeletal development, a pth4 knockout (pth4KO) zebrafish line was generated using CRISPR/Cas9 and transcriptomic profiling was conducted across six key tissues: brain, kidney, intestine, gills, scales, and bone. The results obtained demonstrated that the loss of Pth4 led to pronounced disturbances in calcium and phosphate homeostasis, skeletal deformities, and widespread tissue-specific transcriptional alterations. Notably, dysregulation of mineral regulatory genes-such asfgf23,phex, andslc34a1a was particularly evident in the kidney, suggesting disruption of the FGF23-Klotho axis. In parallel, differential expression of extracellular matrix genes (col1a1a,col10a1a,col11a1) and matrix remodeling enzymes (mmp9,mmp13a,mmp2) in bone and scales indicated impaired skeletal remodeling. Together, these findings highlight a pivotal role for Pth4 in the endocrine and local regulation of mineral metabolism and skeletal integrity, expanding our understanding of PTH family functions in vertebrate physiology.

overall_design: For this study 4 pth4ko fish and 4 WT fish were used. Six tissues were sampled from each fish: intestine, brain, kidney, gills, scales and bone. Samples were collected for each tissue from each fish resulting in a total of 48 samples. We then performed differential gene expression analysis comparing the pth4 knockout samples with the WT samples for each tissue

last: Méndez-Martínez

first: Paula

last: Suarez-Bregua

first: Laura

last: Guerrero-Peña

first: Elisa

last: Barreriro-Docío

first: Carolina

last: Costas-Prado

first: Antonio

last: Cobelo-García

first: Josep

last: Rotllant


title: Fusion-positive rhabdomyosarcoma oncofusions share a common interactome

city: Durham

first: Benjamin

middle: Kakimoto

last: Lau

state: NC

address: 3 Genome Court

institute: Duke University

summary: The sole reoccurring oncogenic mutation in the pediatric cancer of fusion-positive rhabdomyosarcoma is a reciprocal translocation giving rise to a transcriptional oncofusion comprised of the N-terminus of the PAX3 transcription factor encoding DNA-binding domains fused in-frame to the C-terminus of the FOXO1 transcription factor encoding a transactivation domain. However, a host of new translocations have been detected in this cancer that are known or predicted to encode a protein comprised of the same PAX3 or its paralog PAX7 N-terminus, but with very different C-terminal fusion partners. How such different oncofusions cause the identical cancer was unknown. Here we show that these oncofusions are functionally interchangeable and engage a common interactome of proteins and activate a core shared transcriptional program. Interestingly, this common interactome contains the C-terminal fusion partners or their paralogs of all tested oncofusions, as well as the C-terminal fusion partner of a novel oncofusion. We thus suggest that oncofusions originate in rhabdomyosarcoma from the same DNA-binding domain fused to proteins within a common interactome, which in turn engages a core set of genes giving rise to this cancer.

overall_design: We used CUT&Tag to assess genome-wide binding of PAX3-FOXO1 and its cofactors in RF4 cells. Specifically, CUT&Tag for anti-Flag was used to probe endogenous PAX3-FOXO1, as well as for PAX3-FOXO1’s cofactors (INO80D, MAML1 and NCOA1), in RF4-flag cells harboring a Flag tag knockin to endogenous PAX3-FOXO1 allele; additionally, CUT&Tag for anti-V5 was used to probe various rhabdomyosarcoma-associated oncofusions in the shP3F1 RF4-flag cells with an ectopically expressed, V5-tagged PAX3-FOXO1, PAX3-INO80D, PAX3-MAML1 or PAX3-NCOA1.

first: G. Greg

last: Wang


title: Macrophage accumulations on the injured pulmonary surface accelerate intrathoracic adhesions

city: Toon

first: Tomohisa

last: Sakaue

address: Shitsukawa

department: Cardiovascular and Thoracic Surgery

institute: Ehime University

summary: We established a novel mouse model of intrathoracic adhesions (IA) to investigate the molecular mechanisms underlying IA formation. RNA sequencing analysis was performed to explore these mechanisms. A 200 μL talc solution was administered into the left thoracic cavity, and the mice were sacrificed at 30 minutes, 3 days, and 9 days post-administration. IA tissues, including the left lung parenchyma and chest wall, were harvested and homogenized using QIAzol lysis reagent. Total RNA was extracted, and the FASTQ file data were trimmed and mapped using the GLC Genomics Workbench. Differential gene expression and enrichment analyses were performed using RNAseq Chef version 1.1.2. According to the bulk RNA analysis, we observed a significant upregulation of genes associated with inflammatory cytokines and macrophage surface markers, including Il6, Ccl2, Il1β, Tgfβ1, Cd163, Cd68, and Cd86, at day 3. Meanwhile, genes related to the extracellular matrix (ECM) and its production processes were significantly upregulated at day 9. Cnet plot showed that the TNF-α and NF-κB signaling pathways were activated during the early phase, while epithelial-mesenchymal transition occurred during the completion phase of IA formation. Ingenuity Pathway Analysis (IPA) on day 3 revealed activation of leukocyte trafficking, maturation, and emigration, along with agranulocyte adhesion and diapedesis.

overall_design: Bulk RNA-seq profiling for talc-induced intrathoracic adhesion (IA) tissues of left thoracic cavities in mice at day 0, 3 and 9 after talc administration.

first: Yu

last: Mori

first: Hironori

last: Izutani


title: 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination [VDJ-HTGTS-Seq]

city: Beijing

first: Xuefei

last: Zhang

address: No.5 Yiheyuan Road, Haidian District

department: Biomedical Pioneering Innovation Center (BIOPIC)

institute: Peking University

summary: RAG endonuclease initiates V(D)J recombination by cleaving recombination signal sequences (RSSs), subsequently repaired by classical nonhomologous end-joining (c-NHEJ). However, 53BP1, as a key DNA damage response (DDR) factor promoting c-NHEJ, is dispensable for V(D)J recombination. Here, we report that 53BP1 orchestrates sequence strength of RAG targets to shape end-joining features during V(D)J recombination. Deficiency of 53BP1, rather than other DDR factors, specifically increases junctional microhomology (MH) of cryptic RSS (cRSS) recombination instead of RSS recombination. Depletion of RIF1 or Shieldin, downstream factors of 53BP1, partially mimics the phenotypes of 53BP1-deficiency. Notably, loss of RNF168, rather than other classical resection and alternative end-joining factors, is sufficient to fully rescue 53BP1-deficiency-mediated increase of junctional MH during cRSS recombination. Remarkably, RAG mutant and RSS score analyses indicate that sequence strength of RAG targets determines the unique roles of 53BP1 in balancing end-joining outcomes. Our findings provide deeper mechanistic insights into DNA damage repair for RAG cleaved on- and off-targets during V(D)J recombination.

overall_design: We performed VDJ-HTGTS-Seq, 3C-HTGTS, ChIP-seq, and  PRO-Seq in different mutants of v-Abl transformed pro-B cell lines to study roles of 53BP1 in V(D)J recombination.

first: Sha

last: Luo

first: Hailiang

last: Zha

first: Zifan

last: Yang

first: Zhichen

last: Wan

first: Ruoxi

last: Kong

first: Ruolin

last: Qiao


title: 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination [PRO-seq]

overall_design: We performed VDJ-HTGTS-Seq, 3C-HTGTS, ChIP-seq, CUT&RUN, and  PRO-Seq in different mutants of v-Abl transformed pro-B cell lines to study roles of 53BP1 in V(D)J recombination.


title: 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination [ChIP-seq]


title: 53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination [3C-HTGTS-Seq]


title: Clostridioides difficile CenIR

status: Public on Apr 08 2026

city: Iowa City

first: Craig

last: Ellermeier

state: IA

address: 431 Newton Road

department: Microbiology and Immunology

institute: University of Iowa

summary: Effect on gene transcript levels upon CRISPRi silencing the BlaIR homologs, CenIR

overall_design: The wild type strain R20291 harboring either a negative control plasmid (guide does not target anywhere in the C. difficile genome) or a CRISPRi-plasmid targeting cenI (cdr20291_0474) was grown in the presence of 1% xylose to induce CRISPRi.

first: Ute

last: Müh

first: David

last: Weiss


title: Targeted spatial transcriptomic profiling of pleural mesothelioma using 10x Genomics Xenium

last: Severson

state: North Carolina

address: 2301 Erwin Road

department: Department of Surgery

institute: Duke University Health System

summary: Targeted spatial transcriptomic profiling was performed on seven formalin-fixed paraffin-embedded pleural mesothelioma tumor samples from four cases using the 10x Genomics Xenium platform. The Xenium Human Immuno-Oncology panel supplemented with 100 additional custom genes selected from known pleural mesothelioma biomarkers and single-cell RNA-seq-derived marker genes was used. Raw and processed Xenium files  are provided for each sample. To ensure data integrity with downloaded Xenium files, md5 checksums are provided in 'Xenium_GEO.md5'. This dataset is part of a multi-modality study including matched scRNA-seq, bulk RNA-seq, and Xenium spatial transcriptomics generated from overlapping pleural mesothelioma samples. Related controlled-access sequencing data are available in dbGaP under accession phs004285.

overall_design: Seven pleural mesothelioma tumor sites previously assayed by scRNA-seq were profiled by Xenium in situ targeted transcriptomics. Each sample corresponds to an FFPE tissue section from a defined anatomic site with matched case diagnosis metadata. Key per-sample Xenium output filese are provided containing morphology images, decoded transcripts, segmentation files, and count matrices. Sample identifiers are aligned to dbGaP records to facilitate cross-reference to accession phs004285.

middle: T

first: Sam

last: Freyaldenhoven

first: Ben

last: Wadowski

first: William

middle: G

last: Richards

first: Raphael

last: Bueno

first: Matthew

middle: B

last: Cougar


title: A role for miR-4488 in conditional suppression of ER stress-associated pro-inflammatory responses

city: Rehovot

first: Ester

last: Feldmesser

state: Rehovot

address: POB 25

department: Life Science Core Facilities

institute: Weizmann Institute

summary: ER stress underlies numerous severe pathologies. We have metabolically perturbed normal fibroblasts in order to study the biological roles of microRNAs (miRs) under mild and extended ER stress. We now report that miR-4488 quenches inflammation-associated gene expression in such metabolically perturbed cells. Furthermore, we define miR-4488 as a non-canonical miRNA derived from the expansion segment ES7L of the 28S ribosomal RNA. Generation of miR-4488 requires Dicer, but not Drosha. Moreover, its generation involves the autophagy-lysosome route and is inhibited when this pathway is blocked, thus unveiling an anti-inflammatory role for lysosomes engaged at the onset of stress. Mechanistically, miR-4488 suppresses the expression of NFKB2 and RELB, whose mRNAs specifically associate with miR-4488 exclusively upon stress. This selectivity suggests that miR-4488 may have promise for treating mild ER stress-associated diseases.

overall_design: For the mRNA expression array analysis, total RNA derived from miR-CTRL or miR-4488-transfected HFF were used.

first: Dan

last: Michael

first: Alexander

last: Maman

first: Moshe

last: Oren


title: Evidence for coordinate epigenomic roles for CTCF and histone H3.3 in K27M diffuse midline gliomas

city: Davis

first: Paul

last: Knoepfler

state: CA

address: 1 Shields Ave

department: Cell biology and human anatomy

institute: UC Davis

summary: In this study we identified and characterized key chromatin domains in diffuse midline glioma cells, looking at well known types of domains including super enhancers, bivalent domains, and H3K4me3 broad domains as well as the chromatin states identified by chromHMM. In this context, we identified a key role for CTCF in maintaining H3K27me3 levels at bivalent domains, and demonstrated that the H3.3K27M mutation affects both CTCF localization and H3K27me3 at these regions. We further characterized a functional interaction between H3.3 and CTCF in diffuse midline glioma cells, finding that the H3.3K27M mutation affects CTCF localization, leading to an expansion of CTCF-bound domains including a large number of ectopic CTCF binding sites found in H3.3K27M but not WT cells. We also found that CTCF knockdown increases cell viability in H3.3K27M cells, and affected the expression of a set of genes highly enriched in active chromatin states and likely important for some of the oncogenic properties of these cells. Together, our results identified complex chromatin domains defined by combinations of epigenetic modifications, which may have implications for designing therapy regimens that include multiple epigenetic drugs to more effectively target the numerous changes in chromatin observed in glioma cells with H3.3K27M. We also defined an important role for the structural protein and transcription factor CTCF in influencing the epigenetic landscape and transcriptome in the context of the H3.3K27M mutation in diffuse midline glioma cells.

overall_design: H3K4me3 ChIP-seq was performed in DIPG Line XIII cells.

first: Rachel

last: Klein


title: AKT inhibitor capivasertib reverses EVI1‑driven resistance to venetoclax in acute myeloid leukaemia

city: Dalian

first: Xuehong

last: Zhang

state: Liaoning

address: No. 9 West Section Lvshun South Road, Dalian 116044, Liaoning, China

department: Institute of Cancer Stem Cell

institute: Dalian Medical University

summary: Acute myeloid leukaemia (AML) with MECOM rearrangement is recognized by the World Health Organization as a distinct entity characterized by poor prognosis and aggressive disease progression. We demonstrated that elevated EVI1 expression confers resistance to venetoclax by stabilizing MCL‑1 through activation of the PI3K/AKT signalling pathway in vitro. Mechanistically, elevated EVI1 levels were associated with increased phosphorylation of MCL-1 at threonine 163 (T163pMCL‑1), thereby stabilizing MCL-1 by attenuating its ubiquitin–proteasome mediated degradation. Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient-derived primary AML samples with high EVI1 expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1-mediated venetoclax resistance through PI3K/AKT-driven MCL‑1 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high-risk AML subset.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Control and EVI1-overexpressing cells in K562 and MOLM14.

first: Jinsong

last: Yan

first: Jiayin

last: Zhou


title: Spatial transcriptomic profiling of TOP2B-driven anthracycline-induced cardiotoxicity in mouse hearts

city: Cleveland

first: Tyler

middle: J

last: Alban

state: OH

address: 9500 Euclid Ave

institute: Cleveland Clinic

summary: Anthracycline-induced cardiotoxicity (AIC) is a major dose-limiting toxicity in cancer patients, traditionally attributed to off-target inhibition of TOP2B in cardiomyocytes. Here, we performed spatial transcriptomic profiling of mouse hearts to investigate the molecular mechanisms underlying AIC and TOP2B-mediated cardiac dysfunction. Using a tamoxifen-inducible, cardiomyocyte-specific human TOP2B transgenic mouse model, we analyzed spatial gene expression changes associated with heart failure phenotypes. Visium spatial RNA sequencing revealed dysregulation of cardiac contractile and metabolic pathways, including MYH6/MYH7 switching, NPPA upregulation, and UCP3 suppression. These data support a model in which TOP2B overexpression disrupts cardiomyocyte homeostasis and contributes directly to heart failure. This dataset provides a spatially resolved transcriptomic resource for studying TOP2B-driven cardiotoxicity and therapeutic intervention strategies.

overall_design: Mouse hearts were collected from control α-MHC-MerCreMer mice, cardiomyocyte-specific TOP2B transgenic mice induced by tamoxifen mice. Formalin-fixed paraffin-embedded (FFPE) heart sections were processed using the 10x Genomics Visium CytAssist Spatial Gene Expression platform. H&E-stained sections were imaged prior to probe hybridization and library construction. Spatial transcriptomic libraries were sequenced on Illumina NovaSeq. Differential spatial gene expression analyses were performed to identify cardiac remodeling, metabolic, and heart failure–associated signatures linked to TOP2B overexpression and anthracycline exposure.

first: Zhao

last: Jianjun

first: Lin

last: Jianhong

first: Alban

last: Tyler

first: Wang

last: Qingzhu

first: Zhang

last: Wanying

first: Bangalore Parthasarathy

last: Prerana

first: Parsai

last: Shikha


title: Spatial transcriptomics of IRF7-dependent pathway in chronic lung allograft dysfunction

city: houston

first: Nirmal

last: Sharma

state: MAtx

address: Baylor college of medicine

institute: Baylor college of medicine

summary: Chronic lung allograft dysfunction (CLAD) remains a major barrier to long-term survival after lung transplantation. This study investigates the role of the type I interferon master regulator IRF7 in virus-induced airway fibrogenesis. Using NanoString GeoMx digital spatial profiling, we performed whole transcriptome spatial analysis of human lung tissue from CLAD, non-CLAD transplant, and non-transplanted normal donor lungs to characterize the spatial gene expression landscape associated with IRF7-dependent fibrotic pathways.

overall_design: Paraffin-embedded lung tissue sections from CLAD (n=5), non-CLAD transplant (n=3), and non-transplanted donor (n=3) lungs were profiled using NanoString GeoMx Digital Spatial Profiler with the Human Whole Transcriptome Atlas (WTA) panel. Regions of interest (ROIs) were selected using fluorescently labeled antibodies against CD31, PanCK (Tumor), and CD45. Each ROI was segmented into CD31+, CD45+, PanCK+ (Tumor), and Full ROI areas of illumination (AOIs). 9-12 ROIs were selected per patient.

first: Banday

last: Mudassir

first: Rahman

last: Mizanur

first: Goda

last: Yasufumi

first: Naito

last: Tatsuhiko

first: Potter

last: Andrew

first: Mallidi

last: Haripriya

first: Surolia

last: Ranu

first: Lee

last: Stefi

first: Rehman

last: Rakshinda

first: Loor

last: Gabriel

first: Hayes

last: Don

first: Sharma

last: Nirmal


title: EPHB2 Drives EMT-Linked Vasculogenic Mimicry and Cervical Cancer Progression via an ERK–ETV4 Transcriptional Program

city: Suzhou

first: Xiaoqin

last: Yang

state: Jiangsu

address: NO. 199 Renai Road

institute: Soochow University

summary: To investigate the biological function EPHB2 in the cervical cancer, we established hela cell lines in which the EPHB2 gene has been knocked down by the small interfering RNA (siRNA) technique. Two different siRNAs targeting EPHB2 (KD) were used to knockdown EPHB2 expression in hela cells. A scrambled siRNA (NC) was used as a control. For each sample, three independent biological replicates were performed. Then RNA-Seq experiment was performed by Shanghai Biotechnology Corporation (Shanghai, China).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Hela cells and its KD derivatives (siEPHB2).

first: Wenzhi

last: Jiao

first: Minmin

last: Yu


title: Concurrent genetic and non-genetic resistance mechanisms to KRAS inhibition in CRC

city: Houston

first: Salvador

last: Alonso

state: Texas

address: 1400 Holcombe Blvd, FC10.3030

department: GI Medical Oncology

institute: MD Anderson Cancer Center

summary:
Whole exome sequencing and single cell spatial transcriptomics (CosMx) of patient biopsies show that genetic and non genetic resistance mechanisms often coexist in the same tumor.
We show that targeting the early adaptive changes, characterized by inflammatory reprogramming, synergizes with KRAS inhibition.

overall_design: To identify genetic and non-genetic adaptive programs to KRAS inhibition, we prospectively collected 12 matched pre-treatment and on-treatment (day 7 to day 21) biopsies, as well as 8 post-progression biopsies from CRC patients treated with combined KRASG12C plus EGFR inhibition. Patients received treatment in one of two clinical trials combining sotorasib plus panitumumab, or testing adagrasib with or without cetuximab.

first: Lukas

last: Dow


title: T cell receptor signaling induces expression of lysine demethylase KDM6B to maintain Treg homeostasis [ATAC-seq]

city: Memphis

first: Beisi

last: Xu

state: Tennessee

address: 262 Danny Thomas Pl

department: Center for Applied Bioinformatics

institute: St Jude Children's Research Hosipital

summary: Tregs expressing forkhead box P3 (FOXP3) play crucial roles in maintaining immune tolerance and tissue integrity. EZH2, a histone H3 lysine 27 (H3K27) methyltransferase, is known as a key regulator of Treg identity and suppressive function upon activation. Here, we demonstrate that the H3K27 lysine demethylase KDM6B, which catalyzes the opposing reaction to EZH2, is also required for Treg identity and function after activation. Treg-specific deletion of Kdm6b impaired tissue Treg fate and function. KDM6B was upregulated after T cell antigen receptor signaling in Tregs and contributed to the regulation of Treg-associated gene expression through both direct and indirect mechanisms. A subset of Treg functional genes were direct targets of KDM6B and were co-occupied by FOXP3 at cis-regulatory regions, where KDM6B recruitment limited H3K27me3 accumulation. More broadly, KDM6B-dependent H3K27 demethylation facilitated Treg gene expression programs that supported tissue Treg homeostasis.

overall_design: Resting Treg cells were stimulated with T cell receptor signaling for 3 hours and ATAT-seq was performed to detect chromatin accessibility.

first: Minghong

last: He

first: Yongqiang

last: Feng

first: Jason

last: Mock


title: Transcriptomic profiling of brain tissues from HIV-1 gp120 transgenic mice reveals insights into neuropathogenesis

city: Guangzhou

first: Jinhu

last: Zou

state: Guangdong

address: No. 1023-1063, Shatai South Road, Guangzhou City, Guangdong Province, China

department: Department of Microbiology, School of Public Health

institute: Southern Medical University

summary: Despite tremendous progress with antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) remain prevalent, underscoring the need for effective treatments. Sustained immune activation induced by the HIV-1 glycoprotein gp120 is a proposed mechanism leading to neuronal damage in the central nervous system (CNS). To investigate the gp120-mediated transcriptional changes underlying neuropathogenesis, we performed RNA-sequencing (RNA-seq) analysis on brain tissue samples from HIV-1 gp120 transgenic mice and wild-type (WT) control mice to identify differentially expressed genes (DEGs) in the gp120-expressing brains compared to controls.

overall_design: We performed high-throughput RNA-seq analysis using Illumina NovaSeq 6000 on brain tissues from five 12-month-old HIV-1 gp120 transgenic mice and five age-matched wild-type controls.

first: Xuefeng

last: Gao

first: Hong

last: Cao


title: Nickel exposure disrupts epigenetic repression of developmental genes in mouse embryonic stem cells

city: New York

first: Suresh

last: Cuddapah

state: NY

address: 341 East 25th Street

institute: NYU School of Medicine

summary: Nickel (Ni) is a naturally occurring heavy metal widely found in the environment, but anthropogenic activities such as industrial processes and the widespread use of Ni-containing products have elevated its environmental levels. Ni exposure poses significant health risks, and both vertebrate models and epidemiological studies link it to developmental toxicity. However, the mechanisms underlying Ni-induced developmental toxicity remain poorly understood.  In this study, we investigated how Ni exposure affects pluripotency in mouse embryonic stem cells (mESCs). Ni exposure led to aberrant activation of genes associated with mesodermal and endodermal lineages, while ectodermal genes remained largely unaffected. Despite this induction of lineage-associated genes, key pluripotency genes were not downregulated, suggesting a metastable or incomplete differentiation state. Examination of the underlying mechanisms revealed that Ni exposure induced a loss of the repressive histone modification H3K27me3 at bivalent mesodermal gene promoters, without altering its global levels. Pharmacological inhibition of H3K27me3 demethylases attenuated Ni-induced gene activation, confirming that H3K27me3 loss contributes to this process. ESCs are known to naturally exist as heterogeneous populations that fluctuate between naïve and lineage-primed pluripotent states. Maintaining this balance is essential for proper differentiation. Our findings suggest that Ni exposure disrupts this equilibrium by prematurely inducing mesodermal and endodermal programs. Such dysregulation of early pluripotent states may bias cell-fate decisions and contribute to Ni-induced developmental toxicity, providing a mechanistic link between Ni exposure and developmental toxicity.

overall_design: RNA-seq of E14Tg2A mouse embryonic stem cells maintained in LIF-containing media and treated with 0, 100, 150, 200 uM nickel for 4 or 6 days

first: David

last: Filipovic


title: A decline in skeletal muscle NOX4 abrogates exercise-induced adaptive homeostasis and exacerbates biological ageing

city: Melbourne

first: Tony

last: Tiganis

state: Victoria

address: 23 Innovation Walk, Monash University, Clayton

country: Australia

institute: Monash University

summary: A decline in NFE2L2-orchestrated adaptive homeostasis and oxidative distress are thought to be key features of ageing. In contracting skeletal muscle, the ROS-producing enzyme NADPH oxidase 4 (NOX4) is a potent inducer of NFE2L2 adaptive homeostasis. Here we report that skeletal muscle NOX4 levels decline in aged mice and humans, resulting in abrogated NFE2L2 adaptive homeostasis, increased protein oxidative damage and decreased muscle function. We show that deleting NOX4 in skeletal muscle exacerbates the physiological decline associated with ageing, resulting in overt sarcopenia and frailty, characterised by physical inactivity, increased adiposity, systemic inflammation, whole-body insulin resistance and advanced liver disease in aged chow-fed mice. The systems-wide physiological decline in aged skeletal muscle NOX4-deficient mice could be corrected by restoring NOX4 using viral approaches or activating NFE2L2 downstream with sulforaphane and reinstating adaptive homeostatic responses otherwise induced by exercise. Our findings provide important insights into the basis for the decline in NFE2L2-orchestrated adaptive homeostasis that accompanies physical inactivity with age and identify key mechanisms by which exercise may promote healthy ageing.

overall_design: Gastrocnemius muscle from 21-month old muscle-specific Nox4 knockout mice (MckCre:Nox4 fl/fl) and age-matched Nox4 fl/fl controls. Total RNA was isolated from homogenised mouse gastrocnemius muscle tissue with RNeasy mini kits (Qiagen, Hilden, Germany) and processed for library preparation (PolyA, unstranded) and sequencing on an Illumina Novaseq PE150 by Azenta Life Sciences (Burlington, MA).

first: Eamon

last: Coughlan


title: NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness [RRCHIP]

city: Chapel Hill

first: DONGHAI

last: WANG

address: 125 Mason Farm Rd

department: Lineberger Comprehensive Cancer Center

institute: University of North Carolina-Chapel Hill (UNC)

summary: R-loop remodelling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer stem cells to sustain self-renewal and malignancy remains poorly understood. In this study, we found that glioblastoma stem cells (GSCs) maintain a highly active R-loop state compared to their differentiated progeny and normal human stem cells. Genome-wide mapping via RR-ChIP-seq revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. To identify key regulators, we profiled the R-loop interactome and identified N-Acetyltransferase 10 (NAT10), an established RNA ac4C-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 is overexpressed in both GSCs and GBM. ac4C RIP-seq on R-loop RNA revealed abundant ac4C-modified R-loops that regulated the GSC genome. Mechanistically, NAT10 catalyzes widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating an open chromatin state to sustain GSC self-renewal through controlling key stemness regulators such as the transcription factor EGR1. NAT10 knockdown suppressed GSC proliferation and maintenance in vitro and attenuated GBM progression in orthotopic xenograft models in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor Remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting this axis in GBM.

overall_design: Briefly, NLS-RNaseH1-D210N-V5 was expressed in GSC, DGC, and NSC cells. Approximately 1×10⁷ cells were harvested and crosslinked with 1% formaldehyde at 37 °C for 15 minutes, followed by RRChIP-seq using an anti-V5 antibody.

first: Xujia

last: Wu

first: Donghai

last: Wang

first: Jeremy

last: Rich


title: NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness [RNA-Seq]

overall_design: NAT10 was knocked down using shRNA, and total RNA was extracted with Trizol reagent, followed by next-generation sequencing to investigate the molecular mechanism of NAT10 regulation in GSC23 and GSC387 cells.


title: NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness [ac4C-RIP-seq]

overall_design: Following NAT10 knockdown in GSC23 or GSC387 cells, R-loop RNA (collected by precipitation method) was extracted as input for RIP using an ac4C-specific antibody, followed by sequencing.


title: NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness

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

overall_design: Refer to individual Series


title: NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness [H3K27ac]

overall_design: NAT10 was knocked down using shRNA, followed by ChIP-seq analysis in GSC23 and GSC387 glioma stem cells.


title: Trisomy 21 drives ADARB1 overexpression and premature RNA recoding in the developing fetal brain

city: New York City

first: Michael

last: Breen

address: 1468 Madison Ave

department: Depts. of Psychiatry, Genetics and Genomic Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: Understanding how chromosome 21 gene dosage contributes to neurodevelopmental and systemic phenotypes in trisomy 21 (T21) remains a fundamental challenge. We performed transcriptome-wide RNA sequencing on fetal cortical and hippocampal tissues from 20 T21 cases and 27 euploid controls collected between 13–22weeks post-conception—a critical period for human brain development. Differential expression analysis revealed 572 dysregulated genes in the cortex and 519 in the hippocampus (FDR < 5%), with significant enrichment for chromosome 21 genes. Functional enrichment analyses highlighted disruptions in neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes was ADARB1, a chromosome 21–encoded RNA editing enzyme, whose overexpression in T21 fetal brain was associated with increased adenosine-to-inosine (A-to-I) editing, including key recoding events in GRIA2 (p.R764G), GRIA3 (p.R775G), and GRIK2 (p.Y571C, p.Q621R). A meta-analysis incorporating nine independent transcriptomic datasets spanning early embryonic and progenitor cell types validated robust chromosome 21 dosage effects, including consistent ADARB1 overexpression. Extending these findings, a meta-analysis of A-to-I editing across datasets revealed widespread over-editing at 3′UTRs and at GRIA3 (p.R775G), a site critical for AMPA receptor desensitization. Together, these results implicate dysregulated RNA editing—driven by ADARB1 overexpression—as a novel post-transcriptional mechanism contributing to fetal neuropathology in T21 and provide a framework for understanding the broader molecular consequences of chromosome 21 dosage sensitivity during brain development.

overall_design:
Transcriptome-wide RNA sequencing was performed on fetal cortical and hippocampal tissues from 21 T21 and 27 euploid controls collected between 13 and 22 weeks post-conception.

UPDATE:
[Jul-24-2026] The titles and characteristics for GSM9091383 and GSM9091384 were corrected.

first: Andy

last: Yang

first: Xuran

first: Miguel

last: Rodriguez de los Santos

first: Ran

last: Tao

first: Daniel

last: Weinberger

first: Joel

middle: E

last: Kleinman

first: Kalina

last: Mihova

first: Gergana

last: Stancheva

first: Radka

last: Kaneva

first: Violeta

last: Dimitrova

first: Vladimir

last: Vladimirov

first: Thomas

last: Hyde

first: Joseph

last: Buxbaum


title: Effect of endostatin administration on epididymal white adipose tissue gene expression in female mice during the day.

city: San Antonio, TX 78229

first: Christopher

last: Litwin

state: TX

address: 4939 Charles Katz Dr, San Antonio, TX 78229

department: Biochemistry and Structural Biology

institute: University of Texas Health Science Center San Antonio

summary: Endostatin is an endogenous cleavage product of Collagen 18 type a 1, an extracellular matrix protein that has anti-angiogenic properties. Increasing evidence suggests that endostatin has metabolic benefits in obesity models independently from its anti-angiogenic effects. Furthermore, multiple reports have shown drastic reduction in weight gain with endostatin treatment with high fat diet, and cell -autonomous effects of endostatin on adipocytes. The pathways that regulate endostatin 's effects on adipocytes are elusive. We have determined that there is a sex- and time-dependent effect of endostatin on adipose tissue gene expression. Therefore, we treated female mice with endostatin, collected adipose tissue and performed Total RNA-seq on RNA extracted from the tissue.

overall_design: 4 Female mice were treated with 50 mg/kg endostatin or pbs vehicle and tissue was collected 2 hours post-tail vein injection. Food was removed during the post-injection period to account for effects of acute food intake.

first: Kevin

last: Koronowski


title: Multiplex organoid mutagenesis reveals gene combinations driving transformation, pathology and chemosensitivity in ovarian carcinoma

city: Ithaca

first: Coulter

last: Ralston

address: 237 Tower Rd

department: Biomedical Engineering

institute: Cornell University

summary: High-grade serous ovarian carcinoma (HGSC) is the sixth leading cause of cancer-related death among women. Many cases arise from the Fallopian tubal epithelium (TE), exhibit numerous mutations, and present heterogenous pathological features. However, the contribution of specific mutation combinations to cellular transformation, pathological phenotype and chemotherapeutic response remains poorly understood. Here, we used a Trp53-deficient mouse TE-derived organoid platform to perform combinatorial CRISPR mutagenesis of 20 candidate HGSC driver genes. Mutations in Nf1, Cdkn2a and Map2k4 were most frequently observed in transformed organoids. Upon transplantation into mice, those containing Map2k4 mutations predominantly gave rise to papillary-glandular histology, whereas those containing Nf1 mutations formed more mesenchymal-like carcinomas. Transcriptomic analysis revealed that tumors bearing Nf1 mutations overexpressed the long non-coding RNA Pvt1, a marker associated with poor prognosis in HGSC patients, regardless of pathological phenotype Map2k4-mutant organoids were more sensitive to paclitaxel and niraparib, while Nf1-mutant combinations responded better to trametinib. Notably, the removal of Rho kinase inhibitor (ROCKi) reduced trametinib sensitivity in both Map2k4- and Nf1-mutant organoids, underscoring the importance of culture conditions and potential antagonistic drug interactions in organoid-based drug screens. Collectively, our results demonstrate that TE-derived organoids coupled with combinatorial CRISPR mutagenesis provide a powerful system to unravel the genetic and phenotypic complexity of HGSC. In particular, we found that Map2k4 functions as a tumor suppressor that shapes distinct tumor histology and chemosensitivity, suggesting it as a potential therapeutic target in select HGSC cases.

overall_design: RNA-seq analysis to explore how mutation combinations in tubal epithelial organoids drive papillary and mesenchymal tumors after subcutaneous flank injections in mice.

first: Daryl

last: Phuong

middle: R

first: Alexander

middle: Y

last: Nikitin

first: John

last: Schimenti


title: Small regulatory RNAs modulate Lactococcal susceptibility to cell wall-targeting antimicrobials

city: Vilnius

first: Giedrius

last: Vilkaitis

address: Sauletekio av. 7

department: Life sciences center

country: Lithuania

institute: Vilnius Universitye

sample_organism: Lactococcus cremoris subsp. cremoris MG1363


title: Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development

city: Basel

first: Filippo

address: Fabrikstrasse 24,

country: Switzerland

institute: FMI


title: Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development [Hi-C]

summary: Little is known about how three-dimensional chromatin topology shapes mammalian craniofacial development. In mouse cranial neural crest cells, a Polycomb Repressive Complex 2 (PRC2)-dependent chromatin architecture is established before migration. This configuration maintains craniofacial gene promoters poised and connects them with distal Polycomb tethering elements, positioning promoters in spatial proximity to future long-range enhancers. Deletion of Ezh2 disrupts this early topology, causing inappropriate gene derepression in post-migratory craniofacial subpopulations where these genes are normally silenced, and failure of long-range enhancer recruitment where activation is required, thereby impairing proper gene expression. We further identify a distal Polycomb tethering element essential for Hoxa2 enhancer recruitment across topologically associating domains. Thus, Polycomb acts not only as a transcriptional repressor, but also as a chromatin-folding organizer that prepares developmental genes for later activation, by facilitating subsequent recruitment of distal active enhancers previously not in contact. Polycomb-mediated topology therefore orchestrates the transition from progenitor plasticity to precise spatiotemporal control of morphogenetic gene programs during neural crest development and face formation.

overall_design: Hi-C analysis of the 3D chromatin structure in Cranial Neural Crest Cells at developmental stages E10.5 and E11.5 (Md and PA2) WT, Ezh2cKO and Hoxa2-PTE-36kb-del

first: Yousra

last: Ben Zouari

first: Onkar

last: Joshi

first: Adwait

last: Salvi

first: Sandra

last: Kessler

first: Sebastien

last: Ducret

first: Fiona

last: Ross

first: Sojoerd

last: Holwerda

first: Nathalie

last: Vilain

first: Soujanya

last: Mamilla-Sanivaram

last: Smallwood

first: Hubertus

last: Kohler

first: Michael

last: Stadler

first: Maryline

last: Minoux

last: Rijli


title: Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development [PCHi-C]

overall_design: PCHi-C analysis of the 3D chromatin structure in Cranial Neural Crest Cells at developmental stages E8.5, E10.5 and E11.5 (WT, Ezh2cKO, Hoxa2PTE-36kb-del and Hoxa2PTE-42kb-del)

first: Sojoerd J.B.


title: Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development [RNA-seq]

overall_design: RNA-Seq profiling of E11.5 (FNP, Mx, Md and PA2)  cranial neural crest cells WT and Ezh2cKO


title: Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development [ChIP-seq]

overall_design: ChIP-seq (H3K27me3, H3K4me2, H3K27ac and CTCF) profiling of cranial neural crest cell (NCC) progenitors (E8.5) and post-migratory subpopulations (FNP, Mx, Md, PA2; E10.5 and E11.5) of wildtype, Ezh2-conditional knockout, HIRE1 knockout and Hoxa2PTE-36kb-del knockout genotypes.


title: Application of spatial transcriptomics across organoids for a high-resolution spatial whole-transcriptome benchmarking dataset

first: Maria Rosaria

last: Nucera

address: 50, Flemington road

department: Paediatrics

institute: University of Melbourne

summary: Stem cell-derived organoids hold promise to model tissue-specific disease. To enable this, it is crucial to assess how transcriptional signatures, cellular organisation and composition of organoids compare to in vivo counterparts. However, spatial transcriptomics has been challenging to apply to organoids to elucidate regional molecular identity. This study presents the first systematic profiling of multiple stem cell derived organoid models (brain, heart muscle, heart valve, kidney, lung, cartilage, and haematopoietic) with Stereo-seq, a full transcriptome, spatial assay using on-chip in situ RNA capture. It describes assay optimisation for characterisation, use of multiple organoid samples on a single chip, assesses limitations in RNA capture efficiency compared to reference tissues. Furthermore, it introduces a bespoke analysis method that partitions samples into regions for characterisation. These findings inform future works to characterise organoids using spatial transcriptomics, providing insights in optimising RNA capture of multiple organoids across a chip and regional analysis.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We profiled brain, heart, kidney, lung, cartilage, haematopoietic, and engineered heart valve organoids in comparison to mouse E13.5 head and 21 postconceptional weeks (PCW) mouse heart tissue. In addition to multi-organoid placement on a single chip, organoids of the same tissue type cultured under different conditions were co-embedded and profiled on the same Stereo-seq chip.

first: Natalie

last: Charitakis

first: Ryan

middle: F

last: Leung

first: Anna

last: Leichter

first: Natasha

last: Tuano

first: Marzena

last: Walkiewicz

first: Vallari

last: Sawant

first: Lynn

last: Rowley

first: Michelle

last: Scurr

first: Pei

middle: X

last: Er

first: Ker

last: Tan

first: Rebecca

last: Sutton

first: Feroz

last: Ahmad

first: Ritika

last: Saxena

first: Alexander

last: Maytum

first: Declan

last: Turner

first: Holly

last: Voges

first: Hieu

last: Nim

first: Kira

last: Sun

first: Bicheng

last: Yang

first: Nick

last: Li

first: Gareth

last: Ball

first: Andrew

last: Elefanty

first: Shireen

last: Lamande'

first: Kynan

last: Lawlor

first: Jessica

last: Vanslambrouck

first: Richard

last: Mills

first: Elizabeth

last: Ng

first: Edouard

last: Stanley

first: Rhiannon

last: Werder

first: Melissa

middle: H

last: Little

first: David

middle: A

last: Elliot

first: Enzo

last: Porrello

first: Maree

last: Faux


title: Analysis of the mechanism of acquisition of chemotherapy resistance in colorectal cancer cell lines

city: Suita

first: Daisuke

last: Motooka

state: Osaka

address: 3-1, Yamadaoka

institute: NGS core facility, Research Institute for Microbial Diseases, Osaka University

summary: Although anticancer drugs such as fluorouracil and oxaliplatin are widely used in the treatment of colorectal cancer, they are ineffective when cancer cells acquire drug resistance. The treatment strategy for colorectal cancer that has acquired drug resistance has become a problem in chemotherapy. To investigate the cause of drug resistance, we created drug-resistant strains of colon cancer cell lines by mixing a small amount of anticancer drug in the culture medium and culturing them for a long period of time, and explored the genetic changes by RNA-sequence.

overall_design: The colorectal cancer cell lines HCT116, SW480, and DLD1 were exposed to a non-lethal dose of fluorouracil(5 - 70μM) and oxaliplatin(5 - 35μM) and cultured for about 6 months for RNA-seq analysis.

first: Yoshinao

last: Chinen

first: Tsuyoshi

last: Hata

last: Okuzaki

first: Yuichiro

last: Doki


title: Control of Cellular Differentiation Trajectories for Cancer Reversion

status: Public on Apr 07 2026

city: Yuseong-gu

first: Jeong-Ryeol

last: Gong

state: Daejeon

address: 291, Daehak-ro

institute: KAIST

summary: Cellular differentiation is controlled by intricate layers of gene regulation, involving the modulation of gene expression by various transcriptional regulators. Due to the complexity of gene regulation, identifying master regulators across the differentiation trajectory has been a longstanding challenge. To tackle this problem, a computational framework, single-cell Boolean network inference and control (BENEIN), is presented. Applying BENEIN to human large intestinal single-cell transcriptome data, MYB, HDAC2, and FOXA2 are identified as the master regulators whose inhibition induces enterocyte differentiation. It is found that simultaneous knockdown of these master regulators can revert colorectal cancer cells into normal-like enterocytes by synergistically inducing differentiation and suppressing malignancy, which is validated by in vitro and in vivo experiments.

overall_design: RNA-seq profiling of three colorectal cancer cell lines (HCT116, CACO2, and HT29) with scramble shRNA control (NC) and simultaneous shRNA-mediated knockdown of MYB, HDAC2, and FOXA2 (MHF), with two biological replicates per condition.

first: Chun-Kyung

last: Lee

first: Hoon-Min

last: Kim

first: Juhee

first: Jaeog

last: Jeon

first: Sunmin

last: Park

first: Kwang-Hyun

last: Cho


title: T cell receptor signaling induces expression of lysine demethylase KDM6B to maintain Treg homeostasis [RNA-seq]

first: Beisi

last: Xu

overall_design: RNA-seq performed for WT and Kdm6b KO cells in naive and influenza Treg from Lung. A different setting with vs without TCR treating

first: Minghong

last: He

first: Yongqiang

last: Feng

first: Jason

last: Mock


title: T cell receptor signaling induces expression of lysine demethylase KDM6B to maintain Treg homeostasis [CUT&Run]

overall_design: Cut&Run protocol were performed to detect Kdm6b chromatin binding in Treg cells. Each have 2 replicates.


title: Single-cell RNA-seq profiling of pleural mesothelioma and comparator pleural specimens

city: Durham

first: David

last: Severson

address: 2301 Erwin Road

institute: Duke University Health System

summary: This GEO submission contains processed single-cell RNA sequencing data generated using the Seq-Well platform from pleural mesothelioma tumors and comparator pleural specimens. Raw sequencing data are available through controlled access in dbGaP under accession phs004285. Processed expression matrices and cell-level metadata for the single-cell libraries are provided in this submission.

overall_design:
Single-cell suspensions were generated from surgical specimens and profiled by Seq-Well. Sample identifiers in this GEO submission are matched exactly to dbGaP SAMPLE_ID values for cross-reference with controlled-access raw data and associated subject/sample metadata.  Cells were isolated from 93 multi-site resected specimens (113 libraries when separating technical an biologic replicates) and 40 patients. Most specimens were anatomically mapped to six pleural tumor sites, where samples without mapping are denoted with ND. Most sites were also associated with immediately adjacent tissue slides that underwent histopathologic analysis and bulk RNA-sequencing. Patient, sample, site, and associated metadata including tissue type, clinical diagnosis, and features of adjacent tissue or bulk RNA-sequencing are found in "PM_cell_metadata.tsv.gz". Initial QC filtering on technical parameters yielded 266,262 cells. Raw counts from this initial QC analysis are available in 'initial_scRNA_counts_matrix.mtx.gz' (sparse matrix), 'initial_scRNA_geneIDs.tsv.gz' (row gene IDs), and 'initial_scRNA_cellIDs.tsv.gz' (column cell IDs).  To facilitate deeper analysis including identifying malignant cells by inferring CNVs, more stringent filtering was applied including strict cluster-based exclusion of ambient-contaminated and ambiguous cell types described in the methods of the related manuscript, "Multiomic, Histologic, and scRNA-seq Profiling of Pleural Mesothelioma Reveals Negative Prognosis Associated With a Novel Uncommitted Molecular Phenotype" (PMID: 41319863). Strict filtering yielded 93,351 cells. Counts from this highly filtered analysis are available in stringent_scRNA_counts_matrix.mtx.gz (sparse matrix), stringent_scRNA_geneIDs.tsv.gz (row gene IDs), and stringent_scRNA_cellIDs.tsv.gz (column cell IDs). These cells are denoted by the "stringent_filtering" field in cell metadata.
dbGAP, accession phs004285

***************************************************************
Raw files for human/patient samples are being made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) for controlled access to the personally identifiable sequence data.
***************************************************************

first: Sam

last: Freyaldenhoven

first: Ben

last: Wadowski

first: William

last: Richards

first: Raphael

last: Bueno


title: Spatial transcriptomic profiling of human pancreatic ductal adenocarcinoma  using 10x Genomics Visium platform

city: Beijing

first: xin

last: zhao

address: 8#， Gong Ti South Road

institute: Beijing Chaoyang Hospital

summary: In this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma using 10x Genomics Visium spatial gene expression platform. We generated high-quality spatial gene expression profiles combined with histomorphological information, aiming to reveal the spatial heterogeneity of pancreatic cancer microenvironment and identify spatially restricted gene signatures associated with tumor progression. Sequencing was performed on Illumina NovaSeq 6000 platform, and data processing was conducted using SpaceRanger software with hg38 reference genome. The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as “B-cell activation” and “positive regulation of leukocyte activation.” The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+). Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.

overall_design: the study employed the 10x Genomics Visium platform for spatial transcriptomics analysis of normal pancreatic tissue, pancreatic cancer tissue, adjacent tumor tissue, and tumor stroma.

first: Zhangyong

last: Ren

first: Bing

last: Pan

first: Fangfei

last: Wang

first: Shaocheng

last: Lyu

first: Jialei

last: Zhai

first: Xiumei

last: Hu

first: Zhe

last: Liu

first: Lixin

last: Li

first: Ren

last: Lang

first: Qiang

first: Xin

last: Zhao


title: T cell receptor signaling induces expression of lysine demethylase KDM6B to maintain Treg homeostasis

first: Beisi

last: Xu


title: Ocy454 cell gene expression changes with PTH, FAK inhibitor and PDE8A deletion

city: Boston

first: Garyfallia

last: Papaioannou

state: Massachusetts

address: 55 Fruit St

department: Medicine, Endocrine

institute: Massachusetts General Hospital

summary: Cells from the osteocyte cell line Ocy454 were treated with vehicle (DMSO), +/- PTH (100nM), +/- FAK inhibitor (PF431396 10uM) or underwent PDE8A deletion via CRISPR/Cas9. The goal of this study is to determine the similarity between the genes that are differentially expressed with PTH treatment, FAK inhibition and PDE8A deletion and identify common molecular pathways.

overall_design: Ocy454 RNA samples were measured with High Sensitivity RNA ScreenTape analysis (Agilent). High quality RNA samples with RIN > 7 (n = 6) were processed for RNA library construction and sequencing using the Novoseq6000 platform (Novogene). Quality of raw sequencing data was confirmed with quality control using FastQC/0.11.5. Transcripts were quantified using Salmon 100. Salmon index for mouse was generated based on the Ensembl fasta file for GRCm38. Differential expression analysis was performed using DESeq2 101 package based on the criteria of p adjusted value (padj) < 0.05 and log2|FC | ≥ 1.

first: Courney M

last: Mazur


title: Bulk RNA-seq profiling of pleural mesothelioma and comparator pleural specimens

first: David

last: Severson

summary: This GEO submission contains processed bulk RNA sequencing data generated from pleural mesothelioma tumors and comparator pleural specimens. Raw sequencing data are available through controlled access in dbGaP under accession phs004285. Processed gene expression matrices and sample-level metadata for the bulk RNA-seq libraries are provided in this submission.

overall_design:
Bulk RNA sequencing was performed on 89 surgical specimens with either confirmed pleural mesothelioma diagnosis or normal pleura obtained from non-mesothelioma resections. Sample identifiers in this GEO submission are matched exactly to dbGaP SAMPLE_ID values for cross-reference with controlled-access raw data and associated subject/sample metadata.  Raw counts are found in "bulkRNA_rawcounts_matrix.tsv.gz". Raw counts were converted to transcripts per million (TPM) adjusting for gene length and normalized library size using TMM normalization in edgeR. Normalized counts are found in "bulkRNA_TPMcounts_matrix.tsv.gz". Sample metadata is found in "bulkRNA_sample_metadata.tsv.gz".
dbGAP,  accession phs004285

***************************************************************
Raw files for human/patient samples are being made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) for controlled access to the personally identifiable sequence data.
***************************************************************

first: Sam

last: Freyaldenhoven

first: Ben

last: Wadowski

first: William


title: ChREBPα: A Central Metabolic Sensor Driving Lipid Droplet Renewal in Preimplantation Mouse Embryos

city: Teramo

first: Domenico

last: Iuso

address: Via Balzarini 1

country: Italy

institute: Universisty of Teramo

summary: Background: Lipid droplets (LDs) are abundant during early embryogenesis; however, yet, the mechanisms that govern their synthesis, maintenance, and functional relevance remain poorly defined. This study aimed to investigate how early mouse embryos sense lipid depletion and activate adaptive metabolic responses to sustain developmental progression. Methods: Mouse zygotes were mechanically delipidated and cultured under fatty acid free conditions, and LD recovery was quantified by BODIPY staining across development. RNA sequencing was performed at the 2-cell stage embryos to identify transcriptional responses to delipidation. Furthermore, immunofluorescence microscopy, quantitative assays, and functional studies were conducted by the use of inhibitors to investigate molecular actors of LDs de novo synthesis and their role in embryonic survival. Results: Delipidated embryos rapidly regenerated LDs and progressed to the blastocyst stage at rates comparable to controls. Transcriptomic profiling identified ChREBP (Mlxipl) as the principal gene upregulated in response to lipid depletion, with both mRNA and protein levels markedly increased in delipidated embryos. ChREBP displayed dynamic subcellular localization, including nuclear accumulation associated with LD biogenesis and the formation of cytoplasmic foci preferentially localized at the cell cortex and in proximity to endoplasmic reticulum–enriched regions. Partial co-localization of ChREBP with LDs was observed across stages of de novo LD synthesis following delipidation. Furthermore, an association with lipid LDs was observed during active LD regeneration following delipidation. Notably, the inhibition of ChREBP impaired lipid droplet regeneration and resulted in developmental arrest, identifying the morula-to-blastocyst transition as a critical window of sensitivity and the trophectoderm formation as a vulnerable bottleneck Discussion: These findings identify ChREBP as a key metabolic sensor that coordinates LD synthesis and supports normal developmental progression during early embryogenesis, highlighting LDs as critical regulators of early embryonic competence.

overall_design: Rna-seq profiling of 2 cells embryos derived from delipidated and control mouse zygotes.

first: Abdul Majid

last: Khan

first: Dawid

last: Winiarczyk

first: Francesca

last: Boffa

first: Domenica

last: Zbikowska

first: Luca

last: Palazzese

first: Silvestre

last: Sampino


title: Multimodal profiling reveals a Notch-responsive regenerative subpopulation of cochlear supporting cells

city: Omaha

first: Litao

last: Tao

state: NE

address: 2500 California Plaza

department: Biomedical Sciences

institute: Creighton University

overall_design: Refer to individual Series


title: Fate mapping reveals a prenatal-to-neonatal wave of ILC2s with a history of Cd3g expression

city: Oklahoma City

first: Aneta

last: Pankow

state: Oklahoma

address: 825 NE 13th St

department: Arthritis and Clinical Immunology

institute: Oklahoma Medical Research Foundation

summary: Group 2 innate lymphoid cells (ILC2s) are thought to develop in the bone marrow and fetal liver. However, increasing evidence supports the presence of thymic ILC2s in mice and humans. In this study, we introduce a novel fate-mapping mouse model designed to track thymic ILC2s in peripheral tissues. Thymic ILC2s are labeled by ZsGreen whose expression is induced by Cd3giCre. While they are present in the thymus and peripheral tissues, they are not found in the bone marrow. These cells are predominantly abundant during the neonatal stage, when the intense alveolarization and tissue remodeling occur. RNA sequencing revealed elevated expression of cytokine genes, Il13 and Il4, as well as Klrg1 in these cells. They also harbor TCR gene rearrangements suggesting common developmental pathways with T cells. Furthermore, we demonstrate that neonatal ILC2s play a critical role in macrophage polarization in a naphthalene-induced injury lung model. These findings help explore the differences between pediatric and adult immunity and future therapeutic strategies.

overall_design: Thymic DN3 and lung ZsGreen- and ZsGreen+ ILC2s were sorted from 14 days old Cd3giCreRosa26stopZsGreen mice to compare their gene expression profile by bulk RNA sequencing.

first: Xiao-Hong

last: Sun


title: CDK4/6 Inhibition Enhances CAR-T Cell Therapy in Solid Tumors

first: Shom

last: Goel

address: 305 Grattan St

institute: Peter MacCallum Cancer Centre

summary: CDK4/6 inhibitors promote anti-tumor immunity through diverse mechanisms, positioning them as promising adjuvants to cancer immunotherapies. While CDK4/6 inhibitors have demonstrated strong synergy with immune checkpoint inhibitors across numerous preclinical cancer models, their combination with CAR-T cell therapy remains unexplored. In this study, we examined the efficacy of combined CDK4/6 inhibition (trilaciclib) and CAR-T therapy across a range of pre-clinical blood and solid cancer models. In vitro, trilaciclib enhanced human CAR-T cell cytotoxicity and metabolic fitness while reducing expansion. In vivo, the combination outperformed single agents against RB-proficient, trilaciclib-sensitive CD19+ leukaemia. However, in an equivalent RB-deficient model, the combination therapy was no more effective than CAR-T cells alone, suggesting that enhanced CAR-T cell function may be offset by reduced expansion. In contrast, in solid cancer models the combination was consistently more efficacious than either monotherapy. Notably, combination effects were most pronounced in immunocompetent mouse models, including a model with poor sensitivity to trilaciclib as a monotherapy. Mechanistically, CDK4/6 inhibition reduced tumor-infiltrating T-regulatory cells while enhancing CD8+ CAR-T cell persistence, tumor trafficking and cytotoxic function within the tumor. Together, these findings suggest that trilaciclib and CAR-T cell therapy may be an effective combinatorial treatment for solid cancers.

overall_design: HER2-directed mouse CAR-T cells were transferred into immunocompetent C57BL/5 mice 5 days post mammary fat pad inoculation with the mouse breast cancer cell line E0771-hHER2. Mice were treated with continuous 3 days on/4 days off trilaciclib regimen starting the day of CAR-T cell transfer. After 2 cycles of treatment (approximately 14 days after CART cell transfer), CD8+ CAR-T cells isolated from tumors of vehicle- or trilaciclib-treated mice subjected to RNA-sequencing. Differential gene expression analysis was conducted with DESeq2 (v1.36.0) with comparison of Trilaciclib (n=3) versus Citrate (n=3) buffer groups excluding one replicate from the trilaciclib group due to technical issues resulting in an outlier. The package msigdbr (v7.5.1) was used to load genesets from Hallmarks, Kegg and Immunesig. The fgsea bioconductor package (v1.2.0) was used to conduct Gene set enrichment analysis (GSEA) and generate barcode plots.

first: Emily

last: Lelliott

first: Jonathan

last: Naddaf

first: Kun-Hui

last: Lu

first: Katherine

last: Cummins

first: Kelly

last: Ramsbottom

last: Reynolds

first: Michael

last: Taylor

first: Krutika

last: Ambani

first: Isabelle

last: Munoz

first: Susan

last: Jackson

first: Jessica

last: Li

first: Cheok Weng

last: Chan

first: Kara

last: Britt

first: Paul

last: Beavis

first: Jane

last: Oliaro


title: scRNA-seq of mouse cochlea organoid cells

city: Galveston

first: Marie

last: Kubota

address: 301 University Blvd

department: Otolaryngology

institute: University of Texas Medical Branch

summary: Neonatal mouse cochlear epithelium retains regenerative capacity, attributed to the greater epithelial ridge (GER) cells. GER cells proliferate to form organoids and give rise to nascent hair cells and supporting cells. To investigate the growth-promoting pathways in GER cells, we generated organoids from highly enriched mouse GER cells and performed single-cell RNA sequencing. Data analysis revealed changes in gene expression in GER-derived cells during the early growth phase of organoid development. Integrating single-cell RNA sequencing data with in vitro and in vivo functional assays, we identified galectins and Myc activity as essential regulators of GER cell proliferation.

overall_design: We used postnatal day 2 Sox2-GFP/Fgfr3-CreERT2/Ai14-tdTonato transgenic mice to isolate GER cells with flow cytometry. The cells were seeded for organoid formation. Grown organoids were harvested and dissociated at culture days 1, 3, and 7, and analyzed with single-cell RNA sequencing.

first: Julia

middle: M

last: Abitbol

last: Lee

first: Maggie

last: Matern

first: Sonia

last: Bustos Barocio

first: Taha

last: Jan

first: Alan

last: Cheng

first: Stefan

last: Heller