title: Hi-C for genome-wide detection of enhancer-hijacking rearrangements in routine clinical biopsies of lymphoid cancers

city: Ann Arbor

first: Russell

middle: James Hubbard

last: Ryan

state: MI

address: 4306 Rogel Cancer Center, 1500 E Medical Center Dr.

department: Department of Pathology

institute: University of Michigan Medical School

summary: We performed Hi-C retrospectively on archival formalin-fixed paraffin embedded (FFPE) tissue biopsies of lymphoid cancers to explore the utility of Hi-C for comprehensively identifying enhancer-hijacking oncogene rearrangements in routine clinical samples. Our data shows that FFPE-compatible Hi-C retains state-specific topological features of tumor cells at gene loci associated with germinal center B cell or plasma cell state and comprehensively detects rearrangements genome-wide with high concordance against prior clinical testing. Hi-C additionally reveals enhancer-promoter interactions consistent with enhancer-hijacking across rearrangement breakpoints at recurrent, uncommon, and diversely-rearranging loci, and provides topological information to support the interpretation of these events that is not provided by alternative routine clinical assays such as FISH.

overall_design:
Genome-wide chromatin conformation capture (Hi-C) performed on formalin-fixed paraffin-embedded tissue specimens of lymphoid cancers from patients

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Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
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first: Jamin

last: Wu

first: Alec

last: Chu

first: Jang

last: Cho

first: Misha

last: Movahed-Ezazi

first: Kristyn

last: Galbraith

first: Camila

last: Fang

first: Yiying

last: Yang

first: Chanel

last: Schroff

first: Kristin

last: Sikkink

first: Michelle

last: Perez-Arreola

first: Logan

last: Van Meter

first: Savanna

last: Gemus

first: Jon-Matthew

last: Belton

first: Xue

last: Song

first: Aishwarya

last: Gurumurthy

first: Hong

first: Valentina

last: Nardi

first: Abner

last: Louissant Jr.

first: Raju

last: Pillai

first: Joo

middle: Y

first: Dennis

last: Shasha

first: Aristotelis

last: Tsirigos

first: Anamarija

last: Perry

first: Noah

last: Brown

first: Tatyana

last: Gindin

first: Lina

last: Shao

first: Marcin

middle: P

last: Cieslik

first: Minji

last: Kim

first: Anthony

last: Schmitt

first: Matija

last: Snuderl


title: The LncRNA 3222401L13Rik Is Upregulated in Aging Astrocytes and Regulates Neuronal Support Function Through Interaction with Npas3 [young]

status: Public on Jan 12 2026

city: Gottingen

first: Andre

last: Fischer

state: NS

address: Von Sieboldstr 3a

department: Epigenetic Mechanisms in Dementia

country: Germany

institute: German Center for Neurodegenerative Diseases (DZNE)

type: Expression profiling by high throughput sequencing

summary: Aging is linked to a decline in cognitive functions and significantly increases the risk of neurodegenerative diseases. While molecular changes in all central nervous system (CNS) cell types contribute to aging-related cognitive decline, the mechanisms driving disease development or offering protection remain poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular functions and gene expression, yet their roles in aging, particularly within glial cells, are not well characterized. In this study, we investigated lncRNA expression profiles in non-neuronal cells from aged mice. We identified 3222401L13Rik, a previously unstudied lncRNA enriched in glial cells, as being specifically upregulated in astrocytes during aging. Knockdown of 3222401L13Rik in primary astrocytes revealed its critical role in regulating genes essential for neuronal support and synapse organization. This function was also conserved in human iPSC-derived astrocytes. Additionally, we found that 3222401L13Rik mediates its cellular effects through interaction with the transcription factor Neuronal PAS Domain Protein 3 (Npas3), and that overexpression of Npas3 effectively rescued the functional deficits observed in astrocytes lacking 3222401L13Rik. Our findings suggest that upregulation of 3222401L13Rik in aging astrocytes acts as a compensatory mechanism to enhance neuronal and synaptic support, potentially delaying the onset of molecular and structural changes in both astrocytes and neurons. Strategies to boost 3222401L13Rik expression earlier in life may help mitigate age-associated loss of neuronal plasticity.

overall_design: To identify lncRNAs that are deregulated during aging, we isolated the hippocampal CA1 region of 3-  and 16-month-old mice. We isolated neuronal and glial nuclei by performing FACS sorting for NeuN, isolated RNA, generated libraries and performed total RNA sequencing

first: Sophie

last: Schroeder

first: M. Sadman

last: Sakib


title: Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development

city: New Haven

first: Mandar

middle: Deepak

last: Muzumdar

state: CT

address: 333 Cedar Street

department: Genetics

country: USA

institute: Yale University

summary: Pancreatic endocrine-exocrine crosstalk plays a key role in normal physiology and disease and can be altered by host metabolic states, such as obesity. Classically, endocrine islet beta (β) cell secretion of insulin is thought to promote the development of obesity-associated pancreatic adenocarcinoma (PDAC), an exocrine cell-derived tumor. Here, we show that β cell expression of the peptide hormone cholecystokinin (CCK) is necessary and sufficient for obesity-associated PDAC progression in mice and that CCK expression – rather than insulin – correlates strongly with enhanced tumorigenesis. Single-cell RNA-sequencing, in silico latent-space archetypal and trajectory analysis, and experimental lineage tracing in vivo reveal that obesity induces the expansion of postnatal immature β cells, which adapt to express CCK via stress-responsive JNK/cJun signaling. Finally, obesity perturbs CCK-dependent peri-islet exocrine cell transcriptional states and enhances islet-proximal tumor formation. These results define endocrine-exocrine CCK signaling as a bona fide driver of obesity-associated PDAC development and uncover new avenues to target the endocrine pancreas to subvert exocrine tumorigenesis.

overall_design: RNA-seq profiling of pancreata isolated from 12-week old C57BL6/J mice with lean wild-type (WT) mice, obese leptin-deficient (Lep(ob/ob), aka OB) mice, or leptin-deficient (OB) mice treated 6 weeks with CCK-receptor antagonists (CCKR-I, proglumide or lorglumide) drinking water (versus control water), beginning at 6 weeks of age. All mice on standard ad libitum chow diet.

first: Jeremy

middle: B

last: Jacox

first: Christian

middle: R

last: Ruiz

middle: D


title: Study of vitamin D signaling pathways during the initiation of prostate cancer

first: Gilles

last: Laverny

address: 1 rue Laurent fries

country: France

institute: IGBMC

summary: To determine the mechanism underlying the role of VDR in prostatic epitheliales cells during prostate cancer, bulk RNA- sequencing will be performed on sorted luminal cells from PTEN(i)pe-/- and PTEN/VDR(i)pe-/- mouse 1M-3M AGI.

overall_design: Total RNA was isolated from FACS-isolated luminal cells using TRI Reagent (Molecular Research Center, Inc.) and RNeasy Kits (Qiagen). cDNA libraries were generated from 600 ng RNA with an integrity number > 8 using the Stranded mRNA-seq Lib Prep Kit (Illumina), according to the manufacturer’s instructions, quantified and checked for quality using capillary electrophoresis. Fifty base pair single-read sequencing was performed on a NextSeq 2000 (Illumina) following the manufacturer’s instructions. Reads preprocessing steps were performed using cutadapt 1.10, reads were mapped onto the mm10 assembly of Mus musculus genome using STAR version 2.5.3a. Gene expression quantification was performed from uniquely aligned reads using htseq-count version 0.6.1p1, with annotations from Ensembl version 108 and “union” mode. Only non-ambiguously assigned reads were retained for further analyses.

first: Kateryna

last: LEN

last: LAVERNY


title: Assessment of the molecular consequences associated with loss of dysferlin expression in hiPSC-derived muscle cells from LGMD R2 patients.

city: Corbeil-Essonnes

first: Hélène

last: Polvèche

address: 28, Rue Henri Desbruères

institute: I-Stem

summary: LGMD R2 is a rare genetic disorder characterized by progressive proximal muscle weakness and wasting caused by a recessive loss of function of dysferlin, a transmembrane protein controlling plasma membrane repair in skeletal muscles. Despite major advances in biotherapies in recent years, there is currently no curative treatment available for LGMD R2, or dysferlinopathies in general. This failure can be explained in part by our lack of understanding of the functions performed by dysferlin within the muscle fiber. Indeed, despite the identification of dysferlin's role in membrane repair, intracellular vesicular trafficking or calcium homeostasis, we do not know which of these functions or combination of functions is most involved in the pathophysiological development of dysferlinopathies. It also seems highly likely that other dysferlin functions have yet to be discovered. In this aim, we generated hiPSC-derived skeletal muscle model and investigated the molecular consequences associated with loss of dysferlin expression by performing a comparative gene expression profiling between control and LGMD R2 myotubes.

overall_design: 6 samples were analyzed with 3 replicates per condition: 3 WT hiPSC-derived myotubes (control) 3 Limb-Girdle Muscular Dystrophy type R2 (LGMD R2) hiPSC-derived myotubes

first: Céline

last: Bruge

first: Xavier

last: Nissan

first: Margot

last: Jarrige

last: Polveche


title: Hypoxia restores the acidosis-induced inhibition of cancer cell dissemination

status: Public on Jan 11 2026

city: Baltimore

first: Konstantinos

last: Konstantopoulos

state: MD

address: 3400 N Charles St, Croft Hall G65

department: Chemical and Biomolecular Engineering

institute: Johns Hopkins University

summary: Acidosis is a hallmark of the tumor microenvironment and has been linked to aggressive cancer behavior, characterized by increased migration, invasion, and metastasis. We herein demonstrate that short-term exposure (24-72 h) to acidic extracellular pH (pHe=6.4) suppresses cell proliferation, metabolism, dissociation from tumor spheroids, and migration in vitro as well as extravasation in chick embryos and mice. Acidosis acutely inhibits motility by downregulating the activity of sodium-hydrogen exchanger isoform-1 (NHE1), which in turn suppresses phosphatidylinositol 3‑kinase (PI3K)/Akt. PI3K/Akt inhibition blocks Yes-associated protein (YAP) translocation to the nucleus, reducing NHE1 and integrin-linked kinase (ILK) expression. The resulting reduction in NHE1-/ILK-dependent migration and ATP production is rescued by hypoxia across cell types. While certain cancer cells can adapt to long-term (>3 weeks) acidosis and acquire an aggressive phenotype, acidosis-induced adaptation is not universal and depends on the cell’s ability to restrain reactive oxygen species overproduction via fatty acid oxidation.

overall_design: RNA-seq profiling of MDA-MB-231 cells incubated with medium of extracellular pH=7.4 or 6.4 for 24 h or 10 weeks.


title: Aging-associated differences in mammary tumor-initiating populations and immune evasion pathways in breast cancer

city: Boston

first: Kornelia

last: Polyak

address: 450 Brookline Ave. S1070

institute: Dana-Farber Cancer Institute

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

overall_design: Refer to individual Series


title: single-cell RNAseq of splenic germinal center B cells from 8-week-old C57BL/6J mice

city: Nanjing

first: jingjing

last: chen

address: 101 Longmian Road

country: China

institute: Nanjing Medical University

summary: The aim of this study is to characterize the accurate cell cluster of germinal center B cells

overall_design: 0.4×10e6 germinal center B cells were sorted from SRBC immunized C57BL/6J mice  for single cell RNAsequencing.

first: Jingjing

last: Chen

first: Xiaoming

last: Wang


title: single cell analysis from prostates from PTEN(i)pe-/- and PTEN/VDR(i)pe-/-

summary: Prostate cancer (PCa)-related deaths highly corelate with its metastatic spread due to limited efficiency of current therapies. In addition, the cases of de novo metastatic hormone-naïve prostate cancer (mHNPC) are increasing, highlighting the urgent need to identify novel biomarkers and treatment strategies for PCa spread. The impact of vitamin D receptor (VDR) signaling on prostate tumorigenesis remains unknown despite several epidemiologic studies suggesting its preventive role. Here, the consequences of VDR loss in prostatic epithelial cells (PECs) are studied using a relevant mouse model of PCa, Pten(i)pe−/− mice. We show that loss of VDR promotes oxidative stress in prostatic neoplasia that in turn enhances PECs proliferation. Moreover, VDR-loss leads to higher CXCL5 secretion by PTEN-deficient PECs, enhancing immunosuppressive neutrophils infiltration in prostates. Additionally, our data highlight elevated circulating neutrophil levels as a biomarker for PTEN-deficient PCa dissemination to the liver, and show the efficiency of targeting neutrophil chemotaxis to limit cancer spread. Overall, this work demonstrates how vitamin D signaling slows down PTEN-loss driven tumorigenesis and suggests new therapeutic and diagnostic strategies for mHNPC.

overall_design: 2 samples were analyzed, and prepared from dissociated prostates


title: Single-cell resolution drug effects on renin-angiotensin-aldosterone blockade in ZSF1 rat diabetic kidney disease

city: Berlin

first: Michael

middle: S

last: Balzer

address: Charitéplatz 1

department: Dpt. of Nephrology and Medical Intensive Care

institute: Charité - Universitätsmedizin Berlin

summary: Diabetic kidney disease (DKD) is the leading cause of renal failure worldwide. Overactivation of the renin angiotensin-aldosterone system (RAAS) is associated with detrimental outcomes in DKD patients. RAAS inhibitors such as enalapril have been used for decades as antiproteinuric, antihypertensive, and kidney protective agents. Still, the exact cell type of action and the main drivers of drug action are elusive. Here, we leverage state-of-the-art single-cell transcriptomics in the ZSF1 obese rat to elucidate potential target cells and driver molecules exerting enalapril drug effects. We report previously unknown injury cell states of the distal nephron, describe cathepsin D (Ctsd) as an important regulator of enalapril effects, and reveal Trem2+ residential macrophages as top receivers of distal nephron cell-cell communication. Finally, we show that our findings translate to humans and demonstrate that enalapril-associated gene signatures allow stratification of human kidney samples by disease-relevant outcome measures such as kidney function and fibrosis.

overall_design: Single cells were isolated from ZSF1 rat kidneys. N=4 Lean, n=4 Obese, n=3 Obese+enalapril

first: Jianfu

last: Zhou

first: Amin

last: Abedini

first: Ziyuan

last: Ma

first: Yanjuan

last: Hou

first: Tejaswini

last: Yadav

first: Manuel

last: Grundmann

first: Mira

last: Pavkovic

first: Katalin

last: Susztak


title: Aging-associated differences in mammary tumor-initiating populations and immune evasion pathways in breast cancer [scRNA-Seq]

summary: Aging is a major risk factor for breast cancer, yet how it shapes tumor development, molecular phenotype, and immune evasion remains incompletely understood. Deciphering how aging influences cancer development is critical for improving risk assessment, prevention, and treatment. Here, using a N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model that recapitulates key features of human breast cancer, we integrated bulk and single-cell transcriptomics, whole-exome sequencing, and histopathological analysis to dissect age-associated differences in tumorigenesis. We found that age at NMU exposure critically influences tumor incidence, mutational burden, subtype, and immune microenvironment. Tumors arising in aged rats originate from luminal progenitor-like cells with increased genomic instability, suppressed immune infiltration, and impaired antigen presentation linked to loss of heterozygosity at Chr 20p. These age-associated epithelial and immune changes were conserved in human breast cancers, where loss of the homologous Chr 6p region correlated with reduced lymphocyte infiltration and shorter relapse-free survival. These findings reveal that aging alters the tumor-initiating cell population and promotes immune-evasive tumor states through chromosomal instability-driven antigen presentation defects. Our work provides mechanistic insight into the reduced efficacy of immunotherapy in older patients.

overall_design: To induce mammary tumors, rats of different ages (1-, 3-, 6-, 12-, 20-month-old) received two intraperitoneal injections of 50 mg/kg N-Nitroso-N-methylurea (NMU) at a one-week interval. Tumor growth was monitored regularly using caliper measurements. The maximum allowable tumor burden of 4 cm was not exceeded in any experiment. Rats were euthanized by CO₂ inhalation, and tumors were harvested as previously described. Briefly, tumors were enzymatically digested in DMEM/F12 medium containing 2 mg/mL collagenase IV, 2 mg/mL hyaluronidase, and 2 mg/mL bovine serum albumin (BSA) at 37ºC for 1–2 hours, followed by freezing in cryopreservation medium (90% fetal bovine serum (FBS) and 10% dimethyl sulfoxide) in liquid nitrogen. For mammary tumor scRNA-seq, viable cells were resuspended in PBS with 0.04% BSA at a cell concentration of 1000 cells/μL. 10,000 cells were loaded onto a 10x Genomics Chromium™ instrument (10x Genomics) according to the manufacturer's instructions. The scRNA-seq libraries were prepared according to the Chromium Next GEM Single Cell 5’ HT v2 protocol (10x Genomics). Quality control for amplified cDNA libraries and final sequencing libraries were performed using Bioanalyzer High Sensitivity DNA Kit (Agilent). The pooled libraries were sequenced on Illumina NovaSeq X plus platform.

first: Pengze

last: Yan


title: Stiffness sensing fuels matrix-driven metabolic reboot for kidney repair and regeneration [Visium]

status: Public on Jan 10 2026

city: Pittsburgh

first: Shuchang

last: Liu

state: PA

address: 203 Lothrop Street

institute: University of Pittsburgh

summary: Kidney repair after acute kidney injury (AKI) relies on a finely tuned extracellular matrix (ECM) that provides both structural integrity and mechanical cues. As primary ECM architects, fibroblasts and pericytes rapidly mobilize to the injury site post-AKI, yet the ECM-driven repair mechanisms remain inadequately understood. Leveraging data-independent acquisition-based proteomics, spatial transcriptomics, genetic and pharmaceutical models, and tissue engineering, we profiled the proteome landscape of decellularized kidney matrix scaffold post-AKI and highlighted microfibrillar-associated protein 2 (Mfap2) as a key core matrisome component. Sourced primarily from fibroblasts and pericytes, Mfap2 loss disrupts kidney architecture and metabolic balance, aggravating AKI. Global proteomics revealed that Mfap2 knockout downregulates tubule-derived 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) via estrogen receptor 2 (Esr2)-mediated transcriptional repression and elevated post-translational succinylation. Phosphoproteomics further uncovered a shift in mechanical signaling, where Mfap2 deficiency hyperactivates mitogen-activated protein kinases, driving large tumor suppressor kinase 1 (Lats1) in tubular cells without altering integrin receptor activity. Mechanistically, Lats1 suppression amplifies Esr2 transcription without affecting its ubiquitin-mediated degradation, functioning independently of the canonical Yap/Taz signaling. Remarkably, Esr2 agonists restored kidney function in Mfap2-deficient models. These findings position Mfap2 as a key regulator of ECM stiffness and mechanical signaling, orchestrating metabolic reprogramming and a pro-repair microenvironment essential for kidney repair and regeneration.

overall_design: Heterozygous Mfap2 mice (Product name: S-KO-03113, Strain name: C57BL/6JCya-Mfap2em1) were obtained from Cyagen (Santa Clara, CA). Male and female Mfap2 heterozygous mice were mated to generate Mfap2-wild type (WT) and Mfap2-knockout (KO) offspring. Kidney MFAP2 WT slide and MFAP2 KO slide were pooled into one spatial transcritpomics imaging for analysis.

first: Yuan

last: Gui

first: Yuanyuan

first: Wenxue

last: Li

first: Jia-Jun

first: Kelly

last: Zheng

first: Jianzhong

first: Henry Wells

last: Shaffer

first: Cameron

last: Jones

first: Samantha Mae

last: Mallari

first: Yanbao

last: Yu

first: Silvia

first: Yansheng

first: Dong


title: Effect of recombinant human CD26/DPPIV protein or Sitagliptin (DPPIV enzyme inhibitor) on CD3 T cells at day 2 after in vitro cell culture

city: Hefei

first: Liang

last: Wang

state: Anhui

address: 96 Jinzhai Road

institute: University of Science and Technology of China

summary: To examine the impacts of recombinant human CD26/DPPIV protein and Sitagliptin on donor T-cell activation

overall_design: we performed in vitro cell culture assays on T cells selected from PBMCs of healthy donor by adding PHA-L (1.25 μg/mL, control group), PHA-L + recombinant human CD26/DPPIV protein (1000 ng/mL, sCD26 group) or PHA-L + Sitagliptin (DPPIV enzyme inhibitor, 200 μg/mL, Sitagliptin group) for 2 days

first: Yue

last: Wu

first: Yiwen

first: Xiaoyu

last: Zhu

first: Cheng

last: Zhan


title: TWIST1 drives endothelial-to-mesenchymal-transition to stabilize atherosclerotic plaques [single cell RNA-seq]

city: London

first: Paul

last: Evans

address: Charterhouse square

country: United Kingdom

institute: QMUL

summary: Single cell RNA sequencing (scRNA-seq) was used to analyse the diversity of ECs in the atherosclerotic mouse aorta, as well as the effect of endothelial-specific Twist1 deletion on aortic endothelial cells in mice exposed to a high fat diet.

overall_design: 8-10 week old mice were given a high fat diet for 8 weeks. Aftes this, they were injected with tamoxifen for 5 consecutive days to induce gene deletion, and they were fed a high fat diet for 6 weeks longer. The aorta from Twist1 EC-KO mice and  Twist1 EC-WT mice was dissected and digested. Single endothelial cells were isolated by Fluorescence-activated cell sorting (FACS), selecting CD45-, CD31+ and Topro3- cells. Cells were analyzed using scRNAseq.

first: Mark

last: Dunning

first: Blanca

last: Tardajos Ayllón


title: Mineralocorticoid Receptor Antagonism Reduces Atrial Arrhythmias Post- Cardiac Surgery and Attenuates Atrial Stress Responses to Cardioplegic Arrest

status: Public on Jan 09 2026

city: Rochester

first: Ieng Lam

last: Lei

state: MN

address: 321 3rd Ave Sw

institute: Mayo Clinic

summary: We performed snRNA-seq in the left ventricle of human heart from normal control, AF patients, and perfused heart tissue after stored with HTK or HTK+canrenone

overall_design: Nuclei were isolated from the snap frozen tissues, and sequencing in Singleron Platform.

first: Ienglam

last: Tang


title: Replication timing uncovers a two-compartment nuclear architecture of interphase euchromatin

city: Tallahassee

first: Hank

last: Bass

state: FL

address: 222 S Copeland St

department: Biological Sciences

institute: Florida State University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Genome replication is temporally regulated during S phase, with specific genomic regions replicating at defined times in a process that is known as replication timing (RT). Based on 3D cytology in replicating nuclei, we previously proposed a model in which maize euchromatin is subdivided into subcompartments distinguished by chromatin condensation and RT. However, whether this compartmentalization reflects a general nuclear architecture that persists throughout the cell cycle was unclear. To test this model, we conducted two orthogonal assays-Hi-C for genome-wide interaction data and 3D FISH for direct visualization of chromatin organization in maize (Zea mays L.). Hi-C analyses revealed distinct patterns of early-S regions exhibited negative insulation scores with long-range contacts, whereas middle-S regions showed the opposite. Early-S regions showed the strongest correlation with epigenomic signatures of open, transcriptionally active chromatin. 3D oligo FISH painting confirmed that early-S and middle-S replicating regions occupy adjacent but largely non-overlapping nucleoplasmic sub-territories throughout interphase stages, including G1. Together, our findings redefine the maize euchromatin "A" compartment as two spatially distinct subcompartments derived from high-frequency RT transitions between early and middle S along the linear genome. These findings have implications for chromatin-templated processes and underscore the importance of RT as a defining feature of genome organization.

overall_design: Hi-C experiment in maize root tip and earshoot

first: Hafiza-Sara

last: Akram

first: Emily

middle: E

last: Wear

first: Leigh

last: Mickelson-Young

first: Zachary

middle: M

last: Turpin

first: Linda

last: Hanley-Bowdoin

first: William

middle: F

last: Thompson

first: Lorenzo

last: Concia

middle: W


title: Evaluation of targeted and immune combination therapies in a rat model of hormone receptor-positive breast cancer  [scRNA]

first: Kornelia

last: Polyak

summary: Breast cancer hormone receptor (HR) estrogen and progesterone (ER/PR) positive tumors were generated in an outbred rat model (Sprague-Dawley) through the injection of the carcinogen N-nitrosomethylurea (NMU). These tumors were treated with immune checkpoint blockade (anti PD-L1) in combination with targeted therapies, including an TBK1/IKBKE inhibitor, a KMT5B/C inhibitor, a TGF-b inhibitor, and a selective estrogen receptor degrader (SERD). This dataset includes single-cell RNA sequencing (scRNA-seq) data from tumors subjected to various treatment setups. Whole-tumor digestion was performed to preserve a comprehensive representation of the tumor microenvironment. The study aims to identify mechanisms that sensitize HR postive tumor subtypes to immune checkpoint blockade therapy.

overall_design: Tumors were induced by intraperitoneal injection of 50 mg/kg NMU on days 46 and 53 of age. Treatment with NIS793 (a TGFBR inhibitor), IKBKEi (a TNK1/IKBKE inhibitor), A196 (a SUV420H1/SUV420H1 inhibitor), Fulvestrant (an estrogen receptor antagonist), ⍺PD-L1, or a combination of targeted therapy with immune checkpoint blockade (ICB) was initiated when tumors reached 8 mm in size, more than one tumor was detected, or a tumor remained unchanged in size for more than three days. Rats were randomly assigned to treatment groups, and tumor size was measured every other day using calipers.

first: Ernesto

last: Rojas Jimenez

first: Triet

last: Bui

first: Pengze

last: Yan

first: Marco

last: Seehawer

first: Jun

last: Nishida


title: Aging-associated differences in mammary tumor-initiating populations and immune evasion pathways in breast cancer [exome_seq]

overall_design: To induce mammary tumors, rats of different ages (1-, 3-, 6-, 12-, 20-month-old) received two intraperitoneal injections of 50 mg/kg N-Nitroso-N-methylurea (NMU) at a one-week interval. Tumor growth was monitored regularly using caliper measurements. The maximum allowable tumor burden of 4 cm was not exceeded in any experiment. Rats were euthanized by CO₂ inhalation, and tumors were collected and snap frozen in liquid nitrogen. Whole-exome sequencing libraries were prepared using the Agilent SureSelectXT Target Enrichment System following the manufacturer’s protocol. DNA from the liver of an untreated healthy rat served as a normal control. Briefly, 3 µg of genomic DNA extracted from rat tumors was sheared to the desired fragment size using ultrasonication, followed by end-repair, A-tailing, and adapter ligation. The adapter-ligated DNA was hybridized to biotinylated RNA baits targeting exome regions, and captured DNA fragments were enriched using streptavidin-coated magnetic beads. After PCR amplification, the final libraries were quantified, assessed for quality using a Bioanalyzer, and sequenced on an Illumina platform to generate paired-end reads.


title: Multiplexed TrAEL-seq captures DNA replication dynamics in mammalian cells [Bcells]

city: Cambridge

first: Laura

last: Biggins

address: Babraham Research Campus

department: Bioinformatics

institute: The Babraham Institute

summary: TrAEL-seq was used to detect DSBs in mouse B cells activated by treatment with Lipopolysaccharide (LPS)

overall_design: Untreated and LPS activated B cells

first: Alex

last: Whale

first: Claudia

last: Ribeiro de Almeida

first: Jonathan

last: Houseley


title: Aging-associated differences in mammary tumor-initiating populations and immune evasion pathways in breast cancer [bulk_RNA_seq]

overall_design: To induce mammary tumors, rats of different ages (1-, 3-, 6-, 12-, 20-month-old) received two intraperitoneal injections of 50 mg/kg N-Nitroso-N-methylurea (NMU) at a one-week interval. Tumor growth was monitored regularly using caliper measurements. The maximum allowable tumor burden of 4 cm was not exceeded in any experiment. Rats were euthanized by CO₂ inhalation, and tumors were collected and snap frozen in liquid nitrogen. RNA was isolated using RNeasy Mini Kit (Qiagen) with on-column DNA digestion. Two tumors (1m-4 and 6m-1) were excluded from library preparation due to extended postmortem intervals, as the animals were discovered several hours after death. Libraries preparation with poly(A) selection and 150-bp paired-end sequencing on an Illumina HiSeq platform were performed by GENEWIZ (USA; www.GENEWIZ.com).


title: Multiplexed TrAEL-seq captures DNA replication dynamics in mammalian cells

summary: TrAEL-seq was used to detect replication forks and DSBs in PC9 and DLD1 cells in response to Hydroxyurea, DRB Triptolide, Cerelasertib or Palbociclib treatement.

overall_design: PC9 and DLD1 cells, untreated and treated with Hydroxyurea, DRB Triptolide, Cerelasertib or Palbociclib treatment.

first: Kieron

last: May


title: Cocaine, via ΔFosB, remodels gene expression and excitability in ventral hippocampus

city: New York

first: Aarthi

last: Ramakrishnan

state: New York

address: 1425 Madison Avenue

department: Neuroscience

institute: Icahn School of Medicine at Mount Sinai

summary: Ventral hippocampus (vHPC) CA1 pyramidal neurons send glutamatergic projections to nucleus accumbens (NAc), and this vHPC-NAc circuit mediates cocaine seeking and reward, but it is unclear whether vHPC-NAc neuron properties are modulated by cocaine exposure to drive subsequent behavior. The immediate early gene transcription factor ΔFosB is induced throughout the brain by cocaine and is critical for cocaine seeking, but it’s function in vHPC-NAc neurons is not understood. We now show that circuit-specific knockout of ΔFosB in vHPC-NAc neurons impaired cocaine reward expression and forced abstinence-induced seeking. We also found that vHPC-NAc excitability was decreased by experimenter-administered repeated cocaine and cocaine self-administration, and this cocaine-induced excitability decrease was mediated by ΔFosB expression. To uncover the mechanism of this change in circuit function, we used circuit-specific translating ribosome affinity purification (TRAP) to assess cocaine-induced, ΔFosB-dependent changes in gene expression in vHPC-NAc. We found that cocaine causes a ΔFosB-dependent increase in the expression of calreticulin, an ER-resident calcium-buffering protein. Calreticulin expression mediated vHPC-NAc excitability and was necessary for cocaine reward. These findings uncover a novel, non-canonical mechanism by which cocaine increases calreticulin in vHPC leading to decreased vHPC-NAc excitability and drive cocaine seeking and reward.

overall_design: TRAP experiment conducted on saline/coc/cocFlox groups

first: Andrew L.

last: Eagle

first: Marie A.

last: Doyle

first: Chiho

last: Sugimoto

first: Megan

last: Dykstra

first: Hayley M.

last: Kuhn

first: Ian

last: Maze

first: Michelle S.

last: Mazei-Robison

first: Alfred J.

last: Robison


title: Metabolic surgery mitigates early kidney injury in obese youth with diabetes by suppressing mTORC1/JAK–STAT signaling

first: Phillip

middle: John

last: McCown

address: 1500 E. Medical Center Drive

department: Internal Medicine - Nephrology

institute: University of Michigan Medicine

summary: Background Youth with type 2 diabetes (T2D) and severe obesity face high risk of diabetic kidney disease, which metabolic bariatric surgery (MBS) can mitigate. This study explores structural and molecular changes in kidneys after vertical sleeve gastrectomy (VSG), a form of MBS. Methods Paired analyses, including metabolic profiling, kidney volume assessment, histological evaluation, and single-cell RNA sequencing (scRNAseq) on kidney biopsies from five youth with T2D and obesity pre- and 12 months post-VSG in the IMPROVE-T2D (Impact of Metabolic surgery on Pancreatic, Renal and cardiOVascular hEalth in youth with T2D) cohort. Circulating proteomics with kidney transcriptomics, were linked using data from an independent cohort of youth with obesity, with or without T2D, undergoing MBS in Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n=64). Results Post-VSG, participants lost weight and had improvements in insulin sensitivity and metabolic parameters. Kidney changes included reduced renal hyperfiltration, total kidney volume, mesangial matrix area, and microalbuminuria. scRNAseq in proximal tubule (PT) and thick ascending limb cells indicated repression of glycolysis, gluconeogenesis, and tricarboxylic acid cycle genes, with upregulation of AMP-activated protein kinase (AMPK) and Forkhead box O3 (FOXO3). Decreased metabolic signaling aligned with reduced ribosomal phosphorylated S6K (pS6K), suggesting attenuated mTORC1 activity. JAK-STAT pathway activation in PT was diminished, correlating with lower circulating ligands from Teen-LABS proteomic data. Conclusion MBS/VSG prompts kidney molecular adaptations, providing potential targets for non-surgical interventions against obesity- and diabetes-associated kidney disease.

overall_design:
Single cell RNA-seq (scRNA-seq) datasets derived from 10x Genomics processing of segments of kidney biopsied material, preserved in CryoStor, were generated individually and then integrated with harmony-based integration in Seurat v4. Raw data not provided due to patient privacy concerns as a result of small sample size.

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Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
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middle: J

first: Rajasree

last: Menon

first: Abhijit

last: Naik

first: Fadhl

last: Alakwaa

first: Matthias

last: Kretzler

first: Petter

last: Bjornstad


title: Shared cellular characteristics of dysfunctional stromal cell differentiation underpin impaired healing in two models of perturbed fracture healing

first: Kurt

last: Hankenson

address: 109 Zina Pitcher Pl.

department: Department of Orthopaedic Surgery

institute: University of Michigan

summary: 10% of the fifteen million bone fractures each year that occur in the US fail to heal, which leads to significant loss of function, morbidity, and mortality. However, very little is known about the cellular and molecular mechanisms underpinning inferior healing. Two perturbed fracture models, surgically induced ischemia and the genetic deletion of the self-antigen CD47, were studied to identify unifying cellular and molecular mechanisms. C57Bl/6 wild-type (WT) mice with intact vasculature (WT Intact), WT mice with induced ischemia (WT Ischemic), and CD47-null mice with intact vasculature (CD47-KO) underwent transverse tibial fractures. Single-cell RNA-sequencing (scRNAseq) was performed during the inflammatory stage  (4 days post-fracture) and the stromal stage (7 days post fracture) to assess transcriptomic alterations in perturbed fracture calluses.

overall_design: Tibial fractures were performed at 18(±2) weeks of age in C57 Bl/6 mice. A hypodermic needle was first placed as an intramedullary nail followed by tibial fracture using a three-point bend apparatus. Alternatively, mice underwent ischemic fracture by isolation and ligation of the left femoral artery prior to fracture described above. We additionally fractured CD47-null mice on a Bl/6 background. Fracture calluses were harvested at 4 and 7 days post fracture. Periosteum was harvested as well from uninjured WT and CD47-null mice. This represents 8 conditions (1) WT intact vasculature 4 days post-fracture, (2) WT Ischemic 4 days post-fracture, (3) CD47-null intact vasculature 4 days post-fracture, (4) WT intact vasculature 7 days post-fracture, (5) WT Ischemic 7 days post-fracture, (6) CD47-null intact vasculature 7 days post-fracture, (7) WT periosteum, and (8) CD47-null periosteum. For each fracture condition, we sequenced a single biological replicate made up of 8 pooled calluses (equal male/female).

first: Christina

middle: A

last: Capobianco

first: Michelle

last: Song

first: Easton

middle: C

last: Farrell

first: Alexander

last: Knights

first: Karen

last: Kessell

first: Alexis

last: Donneys

first: Tristan

last: Maerz


title: Neuronal Activity Suppresses NEUROD-Dependent Transcription and Genome Organization

city: Evanston

first: Yue

last: Yang

state: IL

address: 2200 Campus Dr

department: Neurobiology

institute: Northwestern University

overall_design: Refer to individual Series

first: Pamela

last: Valnegri

first: Tomoko

last: Yamada


title: DAXX governs the silencing of LINE1 during spermatogenesis in mice [RNA-seq]

city: Wuhan

first: shen

last: jin

state: Hubei

address: No. 299, Bayi Road, Wuchang District, Wuhan City

institute: Wuhan university

summary: The suppression of transposable elements in germline is critical for safeguarding fertility. Here we identify that the DAXX, a potent transcription repressor and an H3.3 chaperone, is indispensable for transposable elements silencing during spermatogenesis. Male mice with conditional knockout of Daxx in germ cells mediated by Ddx4-cre display delayed meiotic progression, deformed and reduced production of sperms, and an age-dependent decline in fertility. The ablation of DAXX results in activation of evolutionarily young LINE1 and ERVs subfamilies. Further study found that reduced H3K9me3 modification and DNA methylation of young LINE1, especially L1Md_A, L1Md_Tf and L1Md_Gf.In summary, this study identifies DAXX as a previously unknown regulator of spermatogenesis and demonstrates that it functions as an epigenetic regulator to maintain the silencing of the young LINE1

overall_design: This study aims to perform RNA-seq profiling to compare the testes of p8 wild-type mice and their knockdown counterparts, thereby exploring gene expression changes during meiosis and sperm development.

first: Zejia

last: Li

first: Chaoyang

last: Xiong

first: Jin

last: Shen

first: Chen

last: Tan

first: Dupeng

last: Ma

first: Jun

last: Chen

first: Rong

last: Liu

first: Qi

last: Sun

first: Weihao

last: Gong

first: Wenming

last: Yuan

first: Mengya

last: Huang

first: Li

first: Yueqiu

first: Guohong

first: Mengcheng

last: Luo


title: Transcriptomic characterization of adipose tissues in cold-exposed mice

city: Changsha

first: Jianlin

last: Zhou

state: Hunan

address: 36 Lushan road

department: College of Life Science

institute: Hunan Normal University

summary: Cold exposure has been shown to induce white adipose tissue (WAT) browning and alter WAT gene expression and lipid metabolism. To understand the transcriptomic profiles of WAT and brown adipose tissue (BAT) upon cold exposure, we performed RNA-seq analysis of inguinal WAT (iWAT) and BAT from mice maintained at either room temperature (RT, 22 °C) or cold (6 °C).

overall_design: RNA-seq analysis of iWAT and BAT from mice maintained at either at 22 °C or 6 °C.

first: Xing

last: Zhang

first: Qiuyan

last: Zhu


title: Neuronal Activity Suppresses NEUROD-Dependent Transcription and Genome Organization [ChIP-Seq]

first: Yue

last: Yang

summary: Neuronal activity induces gene expression programs associated with plasticity in the brain, but it also transiently suppresses gene expression through poorly understood mechanisms. Here, we report that neuronal activity downregulates NEUROD-dependent gene expression in cerebellar granule neurons in adult mice. Using NEUROD1/2 double conditional knockout mice of both sexes, we show that NEUROD binds and activates its target gene enhancers and establishes a three-dimensional genome architecture that facilitates transcription when neuronal activity is low. Moreover, NEUROD antagonizes activity-dependent gene expression programs, including those regulated by MEF2. However, when granule neurons are activated, NEUROD-dependent transcriptional and genome organizing functions are disrupted. Together, these findings reveal NEUROD as a key regulator of transcriptional programs associated with inactive neurons. Our study provides new insights into how neuronal activity reshapes gene transcription and genome architecture in the brain.

overall_design: ChIP-seq libraries using the H3K27ac antibody were prepared from the ADCV of NEUROD1/2 double conditional knockout or control mice. ChIP-seq libraries using the NEUROD1 or NEUROD antibody were prepared from the cerebellum. Libraries were sequenced on the Illumina NextSeq 550 platform to obtain 37 bp paired-end reads. Two biological replicates were performed for all conditions.

first: Pamela

last: Valnegri

first: Tomoko

last: Yamada


title: Regulation of the type I interferon response by chromatin organization (RNA-seq of HoxB8-FL pDC activation)

city: New York City

first: Eduardo

last: Esteva

address: 550 1st Ave

institute: NYU Grossman School of Medicine

summary: Antiviral type I interferons (IFN-I) including IFN-β and multiple subtypes of IFN-α are encoded within a single locus. Whereas most cell types produce primarily IFN-β, plasmacytoid dendritic cells (pDCs) respond to viruses by rapidly producing all IFN-I subtypes. We show that during pDC differentiation, the IFN-I locus translocates from the nuclear periphery and undergoes reorganization of topologically associated domains (TADs). Accordingly, IFN-I production by pDCs was strictly dependent on the TAD-organizing cohesin complex. Promoters of Ifna genes in pDCs were poised, which was imparted by the pDC-enriched transcription factor IRF8. Finally, we identified two distal regulatory regions that facilitated the expression of adjacent IFN-I genes. Thus, the IFN-I response is controlled by multilevel chromatin organization of the IFN-I locus, including its unique poised state in pDCs.

overall_design: RNA-seq was performed on purified HoxB8-FL pDCs stimulated with CpG-A for 6 hours and 24 hours, as well as unstimulated pDCs at the same timepoints as a control (3 replicates per stimulation condition and timepoint).

first: N

last: Adams

first: I

last: Tiniakou

first: E

first: A

last: Khodadadi-Jamayran

first: B

last: Reizis


title: Reconstruction of Extracellular Matrix by Grhl3 Modulates Cell Fate Commitment from Fibroblasts to Induced Cardiomyocytes

first: Xin

last: Wu

address: 115 Donghu Road, Wuchang District

summary: Direct cardiac reprogramming provides a promising therapeutic strategy for heart regeneration by leveraging the endogenous fibroblast population to restore myocardial structure and function. While cardiac transcription factors such as Mef2c, Gata4 and Tbx5 (MGT) drive the generation of induced cardiomyocyte (iCM), the role of extracellular matrix (ECM) components during this process remain largely unexplored. Here, we investigated ECM dynamics during iCM reprogramming and identified integrin subunit alpha 8 (Itga8) as a critical ECM component that suppresses iCM conversion. A loss-of-function screen revealed grainyhead-like protein 3 homolog (Grhl3) as a transcriptional regulator of ECM, including Itga8. Multi-omics analyses demonstrated that Grhl3 efficiency remodels ECM composition to a cardiomyocyte-like state, enhancing iCM reprogramming efficiency and functional maturation. In a mouse model of myocardial infarction, removing Grhl3 enhanced in vivo cardiac reprogramming, and contributed to reduced scar size and improved heart function. These findings establish ECM remodeling as a critical determinant of cardiac reprogramming and identify Grhl3 as a promising therapeutic target to advance myocardial repair strategies.

overall_design: RNA-seq profiling of  cardiac fibroblasts and iCMs treated with shNT/shGrhl3 lentivirus for 5 days;CUT&Tag (H3K27ac)  profiling of  iCMs treated with shNT/shGrhl3 lentivirus for 5 days

last: Wang


title: APEX-seq Maps Transcriptome-wide Subcellular RNA Localization in Living Cells

city: Houston

first: Surbhi

last: Sharma

address: 1840, Dynamic way

institute: Baylor College of Medicine

summary: Although we know a great deal about the subcellular location of most proteins, our knowledge of where most RNAs localize within cells remains limited. As RNA subcellular localization determines the fate, function, and regulation of both coding and non-coding RNAs , there has been substantial interest in developing new scalable approaches to study the location of RNAs in their native context. Furthermore, many locations, such as membrane-bound and membrane-less organelles, have traditionally been challenging to study due to lack of suitable tools to interrogate their constituents. Here, we describe a detailed protocol for APEX-seq that yields transcriptome-wide information of the subcellular address of RNAs that can, in principle, be applied to any subcellular location, membrane, or condensate. APEX-seq utilizes a genetically-encoded engineered ascorbate peroxidase (APEX2) tagged to a specific protein that localizes it to a region of interest. In the presence of biotin-phenol (BP) and hydrogen peroxide, APEX2 catalyzes the biotinylation of RNAs in its vicinity, which can be purified using streptavidin beads and sequenced to reveal the RNA repertoire at that subcellular location. APEX-seq experiments can be carried out by laboratory personnel trained in molecular biology. The analysis of APEX-seq data requires familiarity with standard RNA-seq workflows. With APEX2-expressing cell lines in hand, the entire procedure from labeling reaction to analysis can be completed in one week. We expect this proximity labeling approach to facilitate the unbiased discovery of RNAs localizing to different organelles and to generate hypotheses for the mechanisms and pathways involved in regulating these processes.

overall_design:
APEX-seq was performed in HEK293T cells expressing APEX2 at the outer mitochondrial membrane (OMM). Biotinylated RNA was enriched using streptavidin beads and extracted with TRIzol. RNA-seq libraries were prepared from the enriched RNA using the TruSeq Stranded mRNA Library Preparation Kit. The samples included two labeled targets and two unlabeled controls.
For the ribominus libraries, APEX-seq was performed in HEK293T cells expressing APEX2 in the nucleus (NLS). Biotinylated RNA was enriched using streptavidin beads and released with Proteinase K. RNA-seq libraries were generated using the SMARTer Stranded Total RNA-Seq protocol. These samples also included two labeled targets and two unlabeled controls.

first: Madeline

last: Rasband

first: Xuemei

first: Karen

last: Tolentino

first: Sharon

first: Furqan

last: Fazal


title: Activating and repressive FOX family proteins regulate HSV-1 chromatin and the lytic-latent balance through epigenetic modulators

city: Bostin

first: Don

last: Coen

state: MA

address: 25 Shattuck St

institute: Harvard Medical School

summary: Herpes simplex virus 1 (HSV-1) switches between lytic and latent infections in neurons, yet the switch mechanisms remain obscure. Here we identify forkhead box (FOX) family proteins that can strongly activate or repress HSV-1 replication particularly in neuronal cells. Expression of activating FOX genes (Foxa, Foxc, Foxe, Foxf) is ordinarily low and expression of repressive FOX genes (Foxk) is high in neurons. Lytic HSV-1 infection and other stresses can increase activating FOX gene expression. Such overexpression or knockout of endogenous FOXK1 promotes reactivation from latency. These FOX proteins broadly associate with the viral genome and regulate viral gene transcription through epigenetic modulators. FOXF1 associates with histone acetyltransferases CBP and P300 to open viral chromatin. FOXK1 collaborates with SIN3A, a known cofactor of histone deacetylation, and MAX to suppress HSV-1 replication and antagonize activating FOX proteins. Thus, HSV-1 uses FOX family members with opposing effects to regulate the lytic-latent balance.

overall_design: RNA-seq profiling of human iNGN3 iPSC derived neuronal cells mock or HSV-1 infected under lytic conditions.

first: Dongli

last: Pan

first: Donald

first: David

last: Knipe

first: Biswajit

last: Das

first: Yao Yu

last: Yeo

first: Jean

last: Pesola

first: Pritha

last: Sen


title: DAXX governs the silencing of LINE1 during spermatogenesis in mice [BiSulfite-seq]

status: Public on Jan 08 2026

first: shen

last: jin

type: Methylation profiling by high throughput sequencing

overall_design: This study uses whole-genome bisulfite sequencing (WGBS) to characterize DNA methylation dynamics in the testes of P8 wild-type and knockdown mice, with a specific emphasis on methylation changes across genomic regions and transposable element families.

first: Zejia

last: Li

first: Chaoyang

last: Xiong

first: Jin

last: Shen

first: Chen

last: Tan

first: Dupeng

last: Ma

first: Jun

last: Chen

first: Rong

last: Liu

first: Qi

last: Sun

first: Weihao

last: Gong

first: Wenming

last: Yuan

first: Mengya

last: Huang

first: Li

first: Yueqiu

first: Guohong

first: Mengcheng

last: Luo


title: Single nucleus transcriptomic analysis of osimertinib-induced cardiac dysfunction in the mouse heart

city: Duarte

first: June-Wha

last: Rhee

address: 1500 E Duarte Rd

department: Division of Cardiology, Department of Medicine

institute: City of Hope

summary: We performed single nuclei RNA sequencing (snRNA-seq) analysis of mouse left ventricular tissues to investigate transcriptomic changes caused by osimertinib treatment.

overall_design: Eight mouse snRNA-Seq libraries were prepared from four treatment groups (n=2 per group) – Sham, Osimertinib (Osi), Transverse aortic constriction (TAC), and TAC-Osi – using Next GEM 10x Genomics Chromium Single Cell 3' Reagent Kit v3.1 chemistry, and sequenced on Illumina NovaSeq 6000 at Translational Genomics Research Institute (TGen), an affiliate of City of Hope.


title: KDM5 protein mediated cisplatin resistance in ovarian cancer. [ChIP-Seq]

city: Incheon

first: So Hee

last: Kwon

address: 85, Songdogwahak-ro, Yeonsu-gu

department: Pharmacy

country: South Korea

institute: Yonsei University

summary: High recurrence and relapse rates of ovarian cancer (OVC) make it one of the deadliest gynecological cancers and the 5th most common cause of death in women. It is well recognized that acquired resistance is accompanied by abnormal alteration of epigenetic regulation, yet there is a lack of in-depth mechanistic study on cisplatin-resistant OVC in epigenetic context. Herein, we investigate the role of lysine lysine demethylase 5 (KDM5) and how its abnormal overexpression correlates with cisplatin resistance and OVC tumor progression.

overall_design: ChIP-seq profiling of changes in H3K4me3 observed in cisplatin sensitive ovarian cancer cells (SKOV-3) and cisplatin-resistant ovarian cancer cells (SKOV-3 CDDP), SKOV-3 CDDP KDM5B knockout cells.

first: Jung

last: Yoo


title: The Drosophila proventriculus lacks stem cells but compensates for age-related cell loss via endoreplication-mediated cell growth

city: Boston

first: Yanhui

last: Hu

address: 77 Avenue Louis Pasteur

summary: Drosophila’s proventriculus, a bulb-shaped organ between the foregut and midgut, aids ingestion, peritrophic membrane synthesis, and immune defense. We created a single cell transcriptional atlas of the proventriculus using single nucleus RNAseq (snRNAseq)to to identify molecular markers and use it as the foundation for for further molecular study in various proventriculus cell types.

overall_design: Proventriculus from control and cachectic flies were sequenced separately, then bioinformatically pooled to make an atlas of the tissue.

first: Ben

last: Ewen-Campen

first: Norbert

last: Perrimon


title: Potassium ion homeostasis modulates mitochondrial function

city: South San Francisco

first: Adam

middle: James

last: Waite

state: CA

address: 1170 Veterans Blvd

institute: Calico Life Sciences LLC

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


title: A Glycolytic Shunt via the Pentose Phosphate Pathway is a Metabolic Checkpoint for Nervous System Sensory Homeostasis and Axonal Regeneration

first: Yayue

last: Song

address: Burlington Danes, Hammersmith Hospital, Imperial College London

institute: Imperial College London

summary: Homeostasis and repair in the nervous system are thought to rely on distinct molecular programs. Here, we uncover an unexpected role for the pentose phosphate pathway (PPP) in peripheral sensory axons, where it supports both homeostatic mechanosensation and injury-induced axonal regeneration. We show that the PPP is enriched and active in sciatic nerve axoplasms, where it maintains redox balance via NADPH production, enabling normal mechanical sensation. Following sciatic nerve injury, the PPP is required for regeneration by fueling ribonucleotide synthesis through ribose-5-phosphate production. In contrast, this pathway remains inactive after spinal cord injury (SCI), contributing to regenerative failure. Reactivation of the PPP, through neuronal transketolase overexpression or oral ribose supplementation, promotes metabolic reprogramming, restores sensory and motor axonal growth, and improves neurological recovery after SCI. These findings reveal a dual role for the PPP as metabolic rheostat in sensory neuron physiology and regeneration and highlight its therapeutic potential for central nervous system repair.

overall_design: RNA sequencing profiles of 8 weeks C57BL/6J mice with either AAV-GFP or AAV-Tkt virus injected through scaitic nerves for 4 weeks, L4-6 dorsal root ganglia neurons were extracted 72hr following SCI. RNA sequencing profiles of 8 weeks C57BL/6J mice L4-6 dorsal root ganglia neurons were extracted 72hr following SCI with either 10% ribose or vehicel treatment.

first: Simone

last: Di Giovanni


title: Neuronal Activity Suppresses NEUROD-Dependent Transcription and Genome Organization [Hi-C]

first: Yue

last: Yang

overall_design: Hi-C libraries were prepared from the ADCV of NEUROD1/2 double conditional knockout or control mice. Libraries were sequenced on the Illumina NextSeq 550 platform to obtain 37 bp paired-end reads. Three biological replicates were performed for all conditions.

first: Pamela

last: Valnegri

first: Tomoko

last: Yamada


title: Neuronal Activity Suppresses NEUROD-Dependent Transcription and Genome Organization [RNA-Seq]

overall_design: RNA-seq libraries were prepared from the ADCV of NEUROD1, NEUROD2, or NEUROD1/2 conditional knockout mice or control mice. Additional RNA-seq libraries were prepared from the ADCV of optostimulated or homecage control mice using the chromatin fraction. Libraries were sequenced on the Illumina NextSeq 550 platform to obtain 37 bp paired-end reads. Two to five biological replicates were performed for all conditions.


title: DAXX governs the silencing of LINE1 during spermatogenesis in mice [ChIP-seq]

first: shen

last: jin

overall_design: Genome-wide H3K9me3 ChIP-seq profiling was conducted in meiotic cells and round spermatids from adult wild-type and knockdown mice to assess changes in heterochromatin organization, including at transposable element–associated loci.

first: Zejia

last: Li

first: Chaoyang

last: Xiong

first: Jin

last: Shen

first: Chen

last: Tan

first: Dupeng

last: Ma

first: Jun

last: Chen

first: Rong

last: Liu

first: Qi

last: Sun

first: Weihao

first: Wenming

first: Mengya


title: Landscape of allele-specific expression in prostate cancer reveals recurrent, stage-specific events in AR signaling and resistance pathways [ChIP-Seq]

city: San Francisco

first: Franklin

last: Huang

address: 513 Parnassus Ave

department: Hematology and Oncology

institute: UCSF

summary: The effects of cis-regulatory alterations in prostate cancer (PCa) are insufficiently characterized, presenting an opportunity to discover driver genes and therapeutic targets. To comprehensively study these effects, we identify genes undergoing allele-specific expression (ASE) in localized PCa and metastatic castration-resistant PCa (mCRPC) samples. By defining recurrent ASE events across prostate tissue and tumor-enriched ASE, we develop CASEDI, a computational framework for prioritizing cancer drivers by integrating ASE and clinical data. CASEDI reveals genes showing recurrent ASE and altered expression in PCa, including AR-regulated and oncogenic ACSM1. mCRPC samples show enrichment of ASE in DNA repair, resistance pathways, and oncogenes and increased frequency of monoallelic expression (MAE) compared to localized tumors.  We define an mCRPC gene signature based on MAE status that identifies a subgroup of localized patients with worse prognosis. Using ASE analysis, we expand the landscape of cis-regulatory events in PCa to inform the identification of additional therapeutic targets.

overall_design: ChIP-seq for H3K27ac in MDAPCA2B cells in both control and synthetic androgen (R1881) treatment conditions

first: Margaret

last: Tsui

first: Rebecca


title: Landscape of allele-specific expression in prostate cancer reveals recurrent, stage-specific events in AR signaling and resistance pathways [RNA-Seq 2]

overall_design: Bulk RNA-seq of LNCaP cells treated with synthetic androgen (R1881) and control cells treated with 1% ethanol


title: Landscape of allele-specific expression in prostate cancer reveals recurrent, stage-specific events in AR signaling and resistance pathways [RNA-Seq 1]

overall_design: Bulk RNA-seq of LNCaP cells overexpressing ACSM1 and LacZ control

first: Lorraine

last: Nuniz


title: Programming of the Endometrial Immune Milieu by Interferon Gamma during Early Pregnancy in Pigs

city: Columbia

first: John

last: Driver

state: MO

address: 1201 Rollins Street

institute: University of Missouri

summary: Release of interferon-gamma (IFNG), a pro-inflammatory type II interferon, by the early conceptus is critical for pregnancy establishment in the pig. Yet, the cellular and molecular mechanisms underpinning conceptus-derived IFNG actions in maternal peripheral immune cells and at the embryo–maternal interface remain unclear. Here we show that pregnancy status up-regulates expression of IRF1, an IFNG target-gene, in peripheral blood mononuclear cells on day 15 of pregnancy in the pig. In a second study, loss-of-function IFNG (IFNG–/–) embryos were generated by using CRISPR/Cas9 gene editing and somatic cell nuclear transfer. Single-nuclei RNA sequencing of endometrium from gilts carrying wild-type (Control) or IFNG–/– conceptuses on day 15 of pregnancy revealed cell-type-specific signatures at the embryo–maternal interface in response to conceptus IFNG. Changes in the transcriptome of epithelial and IFNG receptor-expressing immune cells were evident between Control and IFNG–/– samples, along with a downregulation of IFNG target-genes involved with chemotaxis and immune cell differentiation in IFNG–/– recipient endometria. A notable reduction in monocytes and macrophages was observed in IFNG–/– samples, confirmed by immunohistochemistry for AIF1. Differential gene expression (DEG) analysis revealed 391 DEGs in monocytes, implicating IFNG in macrophage polarization, with evidence suggesting a shift toward an M2 phenotype. The study concludes that conceptus IFNG plays an important role in monocyte recruitment and macrophage polarization at the embryo–maternal interface for regulation of inflammation upon conceptus attachment. Insufficient numbers or skewed IFNG-activated macrophages within the endometrium may contribute to pregnancy failure in the IFNG–/– pig model.

overall_design: On day 15 of estrous cycle/pregnancy, recipient (IFNG-/- and IFNG+/+) and bred gilts were euthanized via jugular injection of pentobarbital sodium and phenytoin sodium. The reproductive tracts were excised and transported to the laboratory for immediate processing. Uterine horns were trimmed free of adjacent tissues and processed for sample collection. After flushing and recovery of stage-matched conceptuses to confirm pregnancy, uterine horns were opened longitudinally along the antimesometrial line and endometrial fragments were dissected from the mesometrial side. Tissue samples were snap frozen and stored at −80°C. Prior to flushing, distal parts of each uterine horn near the uterine body were clamped, sectioned transversely, and processed for tissue fixation.


title: Single-cell RNAseq of from murine pancreas tumor (KPC)

city: Woodbury

first: Jonathan

last: Preall

state: NEW YORK

address: 500 Sunnyside Blvd

institute: Cold Spring Harbor Laboratory

summary: Pancreatic ductal adenocarcinoma (PDAC) co-opts the peripheral nervous system through nerve hypertrophy, axonogenesis and perineural invasion, and these processes correlate with patient morbidity and mortality. Prior work has shown that autonomic nerves directly modulate neoplastic cells in PDAC, but whether cancer-associated fibroblasts (CAFs) participate in neural remodeling is unknown. Using thick tissue sections, we identified dense neo-innervation near myofibroblastic CAFs (myCAFs) in preinvasive Pancreatic Intraepithelial Neoplasms (PanINs). Mechanistically, TGF-β produced during inflammation and neoplasia triggers myofibroblast formation, and myCAFs produce axon guidance molecules that recruit sympathetic nerves. Norepinephrine released by sympathetic nerves activates myofibroblast cultures in vitro, and sympathetic nerve depletion impairs stromal activation and PDAC growth in vivo. A chemogenetic model confirmed that fibroblast-specific α1-adrenergic signaling exacerbated pancreatic inflammation and neoplasia. Therefore, beyond direct epithelial effects, sympathetic nerves promote pancreatitis and PDAC by co-opting myofibroblasts and myCAFs as disease amplifiers, highlighting CAF subtype-specific stromal interactions as putative therapeutic targets.

overall_design: Pancreatic tumors from KPC (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) mice were minced and enzymatically digested in DMEM supplemented with Collagenase D, Dispase, DNase I, and soybean trypsin inhibitor at 37°C. KPC tumor suspensions were then stained for CD45,CD31, EPCAM, and FACS sorted. Fibroblasts were enriched by sorting viable (DAPI-) cells from the population negative for all three markers (triple-negative, "TN"). Alternatively, all viable cells were enriched from the DAPI- fraction ("DN").

first: Youngkyu

last: Park

first: Sandeep

last: Nadella

first: Mojdeh

last: Shakiba

first: Jennifer

last: Thalapillil

first: Giuseppina

last: Caligiuri

first: Juliene

last: Hinds

first: Pasquale

last: Laise

first: David

last: Tuveson


title: KLHDC4 serves as a novel prognostic biomarker and drives tumor progression via PI3K/AKT signaling in clear cell renal cell carcinoma

city: Beijing

first: Qingjiang

last: Xu

address: Senior Department of Urology, Chinese PLA General Hospital, Beijing, China.

institute: Chinese PLA General Hospital

summary: The clinical significance and molecular mechanisms of KLHDC4 in malignancies, particularly in clear cell renal cell carcinoma (ccRCC), remain poorly understood. In this study, we integrated multi-omics data—including tran-scriptomic, proteomic, and single-cell RNA sequencing—to systematically evaluate the clinical relevance and func-tional role of KLHDC4, followed by experimental validation. Our results demonstrated that KLHDC4 is significantly upregulated in multiple cancer types and serves as an independent prognostic biomarker for poor survival in ccRCC. KLHDC4 expression was correlated with immune cell infiltration, tumor mutational profiles, and immune check-point expression. Furthermore, KLHDC4 levels predicted response to drug therapies, including immunotherapy and tyrosine kinase inhibitors. Functional experiments showed that KLHDC4 knockdown suppressed proliferation, mi-gration, and invasion in vitro, as well as tumor growth in vivo, whereas its overexpression promoted malignant phenotypes. Mechanistic investigations through RNA sequencing and Western blot analysis indicated that KLHDC4 activates the PI3K/AKT signaling pathway. Rescue assays confirmed that KLHDC4-driven oncogenic effects are partially mediated through this axis. Additionally, molecular docking identified ledipasvir as a potential KLHDC4 inhibitor. Collectively, our findings establish KLHDC4 as a novel prognostic biomarker and therapeutic predictor, highlighting the KLHDC4/PI3K/AKT axis as a potential target for ccRCC treatment.

overall_design: RNA-seq profiling of OSRC-2 cells and their knockdown derivatives(shKLHDC4) at Day2


title: Potassium ion homeostasis modulates mitochondrial function II

first: Adam

last: Waite

summary: Age-associated decline in mitochondrial membrane potential (MMP) is a ubiquitous aspect of eukaryotic organisms and is associated with many aging-related diseases. However, it is not clear whether this decline is a cause or consequence of aging, and therefore whether interventions to reduce MMP decline are a viable strategy to promote healthier aging and longer lifespans. We developed a screening platform in S. cerevisiae to identify mutations that slowed or abrogated the age-associated decline in MMP. Characterization of the longest-lived mutant revealed that reduced internal potassium increased MMP and extended lifespan. Distinct interventions improved cellular MMP and lifespan: deleting a potassium transporter; altering the balance between kinases and phosphatases that control potassium transporter activity; and reducing available potassium in the environment. Similarly, in isolated mitochondria, reducing the concentration of potassium was sufficient to increase MMP. These data indicate that the most abundant monovalent cation in eukaryotic cells plays a critical role in tuning mitochondrial function, consequently impacting lifespan.

overall_design: RNA-seq profiling of WT prototrophic cells grown in complete synthetic media (SC) and sampled either during exponential growth (young) or after 24 hours in a ministat aging device (Hendrickson, 2018).

first: Beiduo

last: Rao

first: Elizabeth

last: Schinski

first: Nathaniel

middle: H

last: Thayer

first: Manuel

last: Hotz

first: Austin

last: Lefebvre

first: Celeste

last: Sandoval

first: Daniel

last: Gottschling


title: Gene expression profile at single cell level of skin cells from back skin of control and Piezo1 inducible knock-out mice

city: Chicago

first: Rui

last: Yi

address: 303 E. Chicago Ave

summary: Piezo1 is a mechanoactive calcium ion channel and is expressed in skin cells. We used single cell RNA sequencing (ScRNAseq) to analyze the functions of mechanical sensing by Piezo1 in hair follicle cells.

overall_design: Hair follicle stem cells were sorted from telogen mouse back skin with a regime of K14H2BGFP+/Cd34+/Itga6+/Sca-1-, then Jun Cut-n-Run were performed on the sorted cells.


title: Nuclear MBL-1 modulates mitochondrial morphology through carnitine palmitoyltransferase in C. elegans with toxic trinucleotide repeats

city: Helsinki

first: Susana

last: Garcia

address: Viikinkaari 5D

department: Institute of Biotechnology

country: Finland

institute: University of Helsinki

summary: Expansion of nucleotide repeat sequences is linked to a growing number of neuromuscular degenerative disorders. Metabolic changes, including disruptions in mitochondrial function and dynamics, characterize these disorders and are believed to contribute to organismal toxicity. To investigate how toxic RNA repeats affect mitochondria, we used a Caenorhabditis elegans model that expresses expanded CUG repeat RNAs in muscle cells and recapitulates muscle dysfunction. We found that the RNA-binding protein Muscleblind-like 1 (MBL-1) is essential for normal mitochondrial function and regulates organelle morphology. In animals expressing expanded CUG repeats, where MBL-1 function is impaired, we identified two distinct mechanisms of mitochondrial disruption: altered mitochondrial morphology regulated by MBL-1, and oxidative phosphorylation (OxPhos) dysfunction occurring independently of MBL-1. Our data further show that changes in mitochondrial morphology are specifically linked to nuclear MBL-1 dysfunction, which affects cpt-3 expression, a gene encoding carnitine palmitoyl transferase—an enzyme required for fatty acid transport into mitochondria. This mechanism is conserved, with similar disruptions observed in patients with Myotonic Dystrophy type 1. Importantly, our findings indicate that mitochondrial disruption does not result from increased organelle fragmentation. Instead, OxPhos dysfunction appears to be a primary contributor to cellular toxicity.

overall_design: Comparison of gene expression profiles between wild-type C. elegans (N2) and muscleblind splicing factor mutant mbl-1(tm1563) at different development stages – as L4s and as 2 days old adults. Comparison of gene expression profiles between C. elegans expressing RNAs with 123CUG repeats in the body wall muscle cells, and controls expressing 0CUGs. Two independent strains of each - 123CUG and 0CUG animals – were analyzed. Animals were analyzed at differential developmental stages: as L4s and as 2 days old adults.

first: Joana

last: Teixeira

first: Mikko

last: Frilander

first: Ove

last: Eriksson


title: Regulation of the type I interferon response by chromatin organization

first: Eduardo

last: Esteva

overall_design: Refer to individual Series


title: Potassium ion homeostasis modulates mitochondrial function I


title: KDM5 protein mediated cisplatin resistance in ovarian cancer.

first: So Hee

last: Kwon

summary: High recurrence and relapse rates of ovarian cancer (OVC) make it one of the deadliest gynecological cancers and the 5th most common cause of death in women. It is well recognized that acquired resistance is accompanied by abnormal alteration of epigenetic regulation, yet there is a lack of in-depth mechanistic study on cisplatin-resistant OVC in epigenetic context. Herein, we investigate the role of lysine lysine demethylase 5 (KDM5) and how its abnormal ovrexpression correlates with cisplatin resistance and OVC tumor progression.

overall_design: RNA-seq profiling of cisplatin sensitive ovarian cancer cells (SKOV-3) and cisplatin-resistant ovarian cancer cells (SKOV-3 CDDP), including their KDM5A and KDM5B double-knockout derivatives.

first: Jung

last: Yoo

first: Enzhi

last: Luo

first: Junjeong

last: Choi


title: A Multi-omic approach reveals iron availability influences hepatocyte cell fate II

city: Melbourne

first: Kristin

middle: K

last: Brown

state: VIC

address: 305 Grattan St

country: Australia

institute: Peter MacCallum Cancer Centre

summary: Recent evidence has highlighted the importance of employing cell culture media designed to reproduce the physiological metabolic environment in vitro. Here, we utilize the physiological medium Plasmax to examine the impact of nutrient availability on the model human hepatocyte cell line, HepG2. Incubation of HepG2 cells in Plasmax suppressed a transcriptional program driven by Hepatocyte Nuclear Factor 4 (HNF4A), a master regulator of hepatocyte identity. Given that HepG2 cells were originally isolated from a patient with hepatoblastoma, this suggests reversion to the native state in physiological media. Importantly, exclusion of the trace element iron from Plasmax reinstated the HNF4A-driven transcriptional program. Taken together, these studies suggest a relationship between iron availability and regulation of hepatocyte cell fate and highlight the importance of more faithfully recapitulating in vivo metabolite availability in vitro.

overall_design: RNA-Seq profiling of HepG2 cells incubated in EMEM, Plasmax, Plasmax without trace elements (Plasmax-TE), and Plasmax without trace elements and with iron supplementation (Plasmax-TE+Fe) for 96 hours.

first: Athena Jessica

last: Ong

first: Andrew

last: Cox


title: A Multi-omic approach reveals iron availability influences hepatocyte cell fate I

overall_design: RNA-Seq profiling of HepG2 cells incubated in low-glucose DMEM (LGDMEM), high-glucose DMEM (HGDMEM), EMEM, and Plasmax for 96 hours.


title: Clinical Characteristics and Spatial transcriptome analysis of Early Resistance to Alectinib in ALK-Positive non-small cell lung cancer: A Retrospective OLCSG Study

city: Okayama

first: Shuta

last: Tomida

state: Okayama

address: 2-5-1 Shikata-cho, Kita-ku

department: Center for Comprehensive Genomic Medicine

country: Japan

institute: Okayama University Hospital

summary: In anaplastic lymphoma kinase (ALK) gene rearrangements positive lung cancer, alectinib has shown good efficacy and is used as a first-line drug. However, some cases show early resistance within 3 months, but the characteristics of these cases have not been established. We analyzed patients with unresectable stage III/IV without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib for primary ALK-TKI. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of Annexin A1 (ANXA1) in the early resistant group.

overall_design: Six cases with surgically resected samples were analyzed using the NanoString GeoMx instrument. Two patients were in the early resistant group and four were in the responder group. 34 ROIs were selected that were representative of each tumor. Immunofluorescence staining was performed using PanCK, CD45, CD68, and SYTO13. We separately profiled RNA from tumor areas (PanCK+). ANXA1, LCN2, and CLDN4 were upregulated in tumor areas with the early resistance group.

first: Tadahiro

last: Kuribayashi

first: Go

last: Makimoto

first: Kadoaki

last: Ohashi


title: Suppression of Notch during efferocytosis prevents macrophages inflammatory polarization [SLAM-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: We investigated the mechanism of suppression of Notch during efferocytosis. Genetically activation of Notch or ablation of Rubicon in marophages induced pro-inflammatory polarization and enhance anti-tumor effect.

overall_design: We performed slam-seq in the presence or abscence of apoptotic Jurkat cells to study how genes expression is regulated during efferocytosis in different genotypes.

first: Zhenrui

last: Li

first: Douglas

last: Green


title: Suppression of Notch during efferocytosis prevents macrophages inflammatory polarization [RNA-seq.HumanMouse]

overall_design: We performed RNA seq and slam-seq in the presence or abscence of apoptotic Jurkat cells to study how genes expression is regulated during efferocytosis in different genotypes.


title: Suppression of Notch during efferocytosis prevents macrophages inflammatory polarization


title: Suppression of Notch during efferocytosis prevents macrophages inflammatory polarization [RNA-seq.Mouse]

overall_design: We performed RNA seq of tumor associated macrophages isolated from wt or notch overactivated mice.


title: Bulk RNA-sequencing of mesenchymal stem cell clones from pig with high or low adipogenic capacity

city: Roslin

first: F. Xavier

last: Donadeu

address: Easter Bush

institute: University of edinburgh

summary: Understanding the molecular regulation of adipogenesis in farm animals would bring benefits both to animal meat production and to the nascent field of cultivated meat, where adipose tissue provides enhanced flavour and texture profiles of biomanufactured meat products. Adipogenic progenitors are found within heterogenous mesenchymal stem cell (MSC) populations in fat and other animal tissues. Such populations contain only a fraction of bona-fide adipocyte progenitors, resulting in limited and variable fat-forming capacity that is highly dependent on animal of origin. The identification of novel markers of pre-adipocytes in species such as the pig would have significant potential towards increasing the efficiency and sustainability of both animal meat production and  cultured fat manufacture. Thus, the aim of this study was to compare the transcriptional signatures of MSC clones with a high or low adipogenic capacity in pig.

overall_design: Comparative bulk RNA-seq analyses was performed of  MSC clones with high or low adipogenic capacy (12 clones each). Clones had been derived by single cell sorting of MSCs from 4 different piglets, and adipogenic capacity was determined by quantitative Oil Red O staining following culture in adipogenic media for 11 days

first: Thomas

last: Thrower

first: Susanna

last: Riley

first: Xavier


title: RNA-seq analysis of low potassium and pmk-1–regulated genes in C. elegans

status: Public on Jan 07 2026

city: Shanghai

first: Rong

last: Huang

address: Shanghai Jiao Tong University, Minhang Campus, 800 Dongchuan Road, Minhang District, Shanghai 200240, China

institute: Shanghai Jiao Tong university

summary: RNA-seq was performed in C. elegans to identify low potassium–responsive genes and pmk-1–dependent genes. Day 1 adult N2 (wild type) or pmk-1(km25) animals were exposed to 100 mM NaCl or 100 mM KCl for 4 hours, and RNA was extracted. Low potassium genes were identified by comparing N2 under 100 mM NaCl versus 100 mM KCl, and pmk-1–regulated genes were identified by comparing pmk-1(km25) mutants to wild type under 100 mM KCl.

overall_design: RNA-seq profiling of synchronized day 1 adult N2 (wild type) and pmk-1(km25) C. elegans exposed to 100 mM NaCl or 100 mM KCl for 4 hours to identify low potassium–responsive and pmk-1–dependent genes.

first: Fangchao

last: Hu

first: Yiyao

first: Qifei

last: Gao

first: Jintao

first: Jiarui

last: Wang

first: Wei

last: Lu

first: Liping

first: Ziyun

last: Wu

first: Keith

last: Blackwell


title: Transcriptional profiling of adipogenic MSC clones in bovine

summary: Understanding the molecular regulation of adipogenesis in farm animals would bring benefits both to animal meat production and to the nascent field of cultivated meat. Adipogenic progenitors are found within heterogenous mesenchymal stem cell (MSC) populations in fat and other animal tissues. Such populations contain only a fraction of bona-fide adipocyte progenitors, resulting in limited and variable fat-forming capacity that is highly dependent on animal of origin. The identification of novel markers of pre-adipocytes in species such as cattle would have signficant potential towards increasing the efficiency and suatainability of both animal meat production and  cultured fat manufacture. Thus, the aim of this study was to compare the transcriptional signatures of MSC clones with a high or low adipogenic capacity in bovine.

overall_design: To investigate the genomic changes in highly adipogenic clones, we performed comparative gene expression analysis on bulk RNA-seq data obtained from 10 non-adipogenic and 10 adipogenic cell clones obtained from 4 different animals.

first: Seungmee

last: Lee

first: Esteves

last: Cristina


title: RNA-Seq analysis of Mapk14 knockout and myogenic differentiation in C2C12 cells

summary: This study investigates the role of p38/Mapk14 in myogenic differentiation using C2C12 mouse myoblast cells. Wild-type and Mapk14 knockout cells in the logarithmic growth phase were cultured in growth medium (GM) or differentiation medium (DM) for 5 days. RNA was extracted for sequencing to examine gene expression changes caused by Mapk14 deletion and by differentiation induction. Differential expression analysis identifies genes downregulated in Mapk14 knockout cells compared to wild type and genes upregulated upon differentiation, providing insight into the molecular mechanisms by which p38/Mapk14 regulates myogenesis.

overall_design: RNA-seq profiling of wild-type C2C12 cells and Mapk14 knockout C2C12 cells cultured under growth medium (GM) or differentiation medium (DM) conditions for 5 days.


title: Tfam-Mediated Metabolic Perturbation in RORgt+ Lymphocytes Impacts Intestinal Tissue Homeostasis and Promotes GATA3+RORgt+ Innate Lymphoid Cells

city: Gainesville

first: Liang

last: Zhou

address: 1945 SW 16th Ave

institute: University of Florida

summary: Rorc-mediated deletion of Tfam, a mitochondrial transcription factor, causes tuft cell-type 2 immunity-driven small intestine (SI) lengthening in mice. Here, we report an indispensable role for Th2 cells in this process. High-fat diet (HFD) reverts SI lengthening in Tfamf/fRorc-cre mice by suppressing IL-13-producing Th2 cells and IL-17-producing Th2 and ILC2s. HFD reduces conventional GATA3–/loRORgt+ ILC3s, but promotes GATA3+RORgt+ ILCs, especially in Tfamf/fRorc-cre mice. Compared to conventional ILC3s, GATA3+RORgt+ ILCs express type 2 cytokines, increase cell proliferation but decrease cell death with metabolic reprograming. Single-cell transcriptional analyses indicate that GATA3+RORgt+ ILCs represent a distinct population, different from IL-17– natural ILC2s, IL-17+ inflammatory ILC2s, or conventional ILC3s. GATA3+RORgt+ ILCs produce IL-17 but not IL-22, resulting from competition of the aryl hydrocarbon receptor (Ahr) with GATA3 at the Il22 locus. Tfamf/fRorc-cre mice on HFD have worsened DSS-induced colitis. These data highlight the role of ILC metabolism in intestinal tissue remodeling and inflammation.

overall_design: Live Lin–CD90.2+CD45.2+ (Lin: CD3, CD5, CD19, B220, TER119, Ly6G) cells were isolated and purified by FACS sorting from large intestine of 8 mice (Tfamf/f CD, n=2; Tfamf/fRorc-cre CD, n=2; Tfamf/f HFD, n=2; Tfamf/fRorc-cre HFD, n=2).

last: Sun

first: Eric

middle: Y

last: Helm

first: John

last: Bostick


title: Hepatic Hypoxia-Inducible Factor 1α Mediates Ferroptosis via Transferrin Receptor 1 in Acute Liver Injury

first: Jingya

last: Li

address: 189 Guo Shou Jing Road

institute: Shanghai Institute of Materia Medica

summary: Acute liver injury (ALI) is a potentially life-threatening condition lacking effective clinical drugs. Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of both inflammation and metabolism. In ALI, HIF-1α expressions are upregulated, but the role of HIF-1α in hepatocytes and whether it can be targeted remain unclear. Herein, clinical samples and ALI murine models including lipopolysaccharide/D-galactosamine (LPS/D-GalN), acetaminophen (APAP), and thioacetamide (TAA) revealed an increase in HIF-1α expression and ferroptosis. Using HIF-1α gain and loss of function mouse and hepatocyte culture models, we demonstrated that HIF-1α upregulation exacerbated liver ferroptosis and injury. Mechanistically, HIF-1α/transferrin receptor protein 1 (TFR1) axis drives hepatic iron overload, promoting ferroptotic cell death and liver injury. In addition, TFR1 inhibition reversed HIF-1α-induced ALI. Importantly, pharmacological inhibition of HIF-1α and TFR1 significantly reduced ferroptosis and mitigated liver injury both in vivo and in vitro. Together, our findings demonstrate the pathological role of hepatic HIF-1α, which may serve as a promising target of therapeutic intervention.

overall_design: RNA Seq profiling of hepatic HIF1α overexpression or wild type mouse livers in control gourps and LPS/D-GalN-treated groups.

first: Shichao

last: Cui

first: Jiayu

last: Yang

first: Meicheng

first: Yulan

last: Xia

first: Yinfang

last: Xie

first: Zhu

first: Ni

first: Xinwen

last: Zhang

first: Pengfei

last: Zhu

first: Xu

last: Yu

first: Linshi


title: Deciphering functional intra-tumoral heterogeneity in BRAFV600E-driven mouse thyroid cancer reveals EMT trajectory and metabolic remodeling

first: Siyi

last: Shen

address: 320 Yueyang Road

institute: Shanghai Institution of Nutrition and Health, Chinese Academy of Sciences

summary: A better understanding of functional heterogeneity of tumor cells may lead to the improvement of the diagnosis and development of effective therapies for patients with papillary thyroid cancer (PTC). Here, the transcriptional heterogeneity and hierarchical trajectory of malignant thyrocytes were investigated by single-cell RNA sequencing analysis in an adult-onset autochthonous mouse model of PTC driven by a BRAFV600E. Within BRAFV600E thyrocytes, we identified distinct subpopulations exhibiting varying degrees of mesenchymal transformation and stability. Further analysis uncovered an epithelial-mesenchymal transition (EMT) trajectory, where malignant subpopulations progress from an intermediate to a more mesenchymal and malignant state. The EMT-related phenotype of each subpopulation was validated with an organoid culture system. Further analysis demonstrated that major malignant subpopulations maintain distinct EMT states through subpopulation-specific pathway usage, whereas transitioning cells undergo a dynamic shift in molecular strategy by using different pathway combinations or distinct gene sets within the same EMT-related pathways along the EMT trajectory. Moreover, metformin diminished the most malignant subpopulation in the PTC mouse model and inhibited EMT potential in both regular and organoid cultures. Importantly, the functional heterogeneity of tumor cells identified in PTC mouse model have clinical relevance. Furthermore, transcriptome dynamics analysis revealed an EMT trajectory-related gene module with substantial predictive value for human PTCs with BRAFV600E. Lastly, our analysis reveals that p53 deficiency lowers the tumorigenic threshold for BRAFV600E and promotes cell state transition towards a more malignant state, rather than altering cellular heterogeneity or the transition trajectory. Subsequent analysis in vitro demonstrated that p53 loss might confer more malignant potential to BRAFV600E thyrocytes through modulating metabolic plasticity. Collectively, our work not only deciphers the functional intra-tumoral heterogeneity of BRAFV600E-drieven PTC but also thereby provides a theoretical foundation for developing EMT-targeted treatment.

overall_design: To uncover intra-tumoral heterogeneity in PTC mouse models, scRNA-seq was performed on thyroid glands from TB or TBP mice 5-7 months after tamoxifen-induced recombination.

first: Hao

last: Ying

first: Ling

first: Jing


title: Patients with AML with WT TP53 but defective TP53-mediated apoptosis have a dismal survival

city: Ann Arbor

first: Karan

last: Bedi

state: MI

address: 1600 Huron Pkwy

department: Biostatistics

institute: University of Michigan

summary: The survival of patients with acute myelogenous leukemia (AML) carrying mutations in TP53 is dismal. We report the results of a detailed characterization of responses to treatment ex vivo with the MDM2 inhibitor MI219, a p53 protein stabilizer, in AML blasts from 165 patients focusing analyses on patients with WT TP53. In total 33% of AML were absolute resistant to MDM2 inhibitor-induced apoptosis, of which 45% carried TP53 mutation and 55% were TP53 WT. We conducted array-based expression profiling of 10 resistant and ten sensitive AML cases with WT TP53 status, respectively, at baseline and after 2 hours and 6 hours of MDM2 inhibitor treatment. While sensitive cases showed the induction of classical TP53 response genes, this was absent or attenuated in resistant cases. In addition, the sensitive and resistant AML samples at baseline profoundly differed in the expression of inflammation-related and mitochondrial genes. No patient with TP53 mutated AML survived. The 4-year survival of AML with defective MDM2 inhibitor-induced TP53-mediated apoptosis despite WT TP53 was dismal, at 19% when NPM1 was comutated and 6% when NPM1 was WT. In summary, we identified prevalent multicausal defects in TP53-mediated apoptosis in AML resulting in extremely poor patient survival.

overall_design: we obtained IC50 values to MDM2 inhibitor treatment in purified AML cell samples.  We selected 10 samples each that were sensitive or resistant and conducted array based expression analysis at baseline (0h), 2h and 6h.

first: Sami

middle: N

last: Malek


title: Targeting Sufu-mediated Gli transcription alleviates ciliopathic phenotypes [kif3a_CUT&RUN]

city: Cincinnati

first: Samantha

last: Brugmann

state: OH

address: 3333 Burnet Ave

department: Developmental Biology

institute: Cincinnati Children's Hospital

summary: Ciliopathies are incurable, pleiotropic diseases that result from defective cilia. Several ciliopathic phenotypes arise from improper processing and activity of Gli transcription factors yet attempts to rescue these phenotypes by overexpressing activator or repressor Gli isoforms have proven unsuccessful. Gli proteins are regulated by Sufu, and Sufu-Gli complexes accumulate in ciliopathies, fundamentally altering the normal Sufu-Gli interaction dynamics. Herein, we investigated whether targeting Sufu-Gli interactions would provide a therapeutic benefit for ciliopathies. We introduced a single copy of SufuD159R, a point mutation that disrupts Sufu-Gli binding, into a ciliopathic mouse model. This genetic modification restored Gli3 binding to DNA and the subsequent transcription of target genes, and led to a significant rescue of numerous ciliopathic phenotypes. These findings suggest that modulating Sufu-Gli interactions may serve as a promising therapeutic approach for ameliorating ciliopathic pathologies.

overall_design: Gli3 CUT&RUN of E11.5 mandibles from wild-type, Kif3a f/f;Gli3 BioFLAG/+;Wnt1Cre knockout mutant and Kif3a f/f;Gli3 BioFLAG/+;Wnt1Cre;SufuD159R+/- embryos.

first: Ching-Fang

last: Chang


title: Expression data from B lymphoid precursors of EPO-exposed and PBS-exposed C57BL/6 mice

city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

institute: GenoSplice technology

summary:
B lymphopoiesis, a critical process during hematopoiesis, is tightly regulated through the expression of specific gene sets. While exposure to erythropoietin (EPO) has been shown to negatively affect B lymphopoiesis in mice, its impact on transcriptional regulation remains poorly understood
Using microarrays, we analyzed gene expression in B lymphoid precursors from control wild-type (C57BL/6) mice and EPO-exposed mice. Our analysis revealed distinct classes of genes that were up-regulated or down-regulated during stress erythropoiesis

overall_design: B lymphoid precursors were FACS-sorted at successive stages of bone marrow lymphopoiesis (Pro-B, Pre-BI, Pre-BII-L, and Pre-BII-S) for RNA extraction and hybridization using Affymetrix microarrays

first: Salima

last: Hacein-Bey-Abina

first: Andrada

last: Chiron


title: GATA4 Ubiquitinated by CRL4B complex to stimulated Lysosome and promote Ovarian cancer EMT process [ChIP-seq]

city: Chongqing

first: Xin

last: Yin

address: 1 Yixueyuan Road, Yuzhong District

institute: Chongqing medical university

summary: GATA4 has emerged as a prominent transcription active factor for cardiomyogenesis and carcinogenesis. Ovarian cancer is a lethal cancer for women due to the hard diagnosis and easy metastasis. However, the role of GATA4 in breast cancer metastasis remains poorly understood. Here, we indicated that GATA4 was decreased in ovarian cancer and associated with excessive lysosome function and epithelial-mesenchymal transition (EMT). Mechanically, GATA4 was ubiquitinated by CUL4B, a submit of Cullin-Ring E3 ligase (CRL) complexes, and decreased the histone H3K27 acetylation. In vivo, knock down GATA4 was facilitated the proliferation and metastasis of SKOV3. RNA-seq and CUT&Tag ChIP-seq of the transcriptional target of the GATA4 and GATA4/CUL4B complex identified a cohort of genes including TRM22 and KLK15 that are potential involved in lysosome and EMT. These results suggest that GATA4 as a tumor suppressor to impair the lysosome acid environment and promote ovarian cancer metastasis in vivo and vitro through ubiquitin degradation system initiated by CRL4B complex. Our study supporting the tumor suppression role of GATA4, implied the pursuit of GATA4 as a therapeutic target for cancer intervention.

overall_design: To investagate the target genes of GATA4 and CUL4B in regulation of ovarian cancer, CUT&Tag ChIP-seq for GATA4 and CUL4B was performed in SKOV3 cells

first: Junlin

last: He


title: A stem cell knockout village reveals lineage rewiring and a non-canonical islet cell fate in monogenic diabetes

city: Washington

first: Bicna

last: Song

state: DC

address: 7144 13th Pl NW

institute: Children's National Hospital

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

overall_design: Refer to individual Series


title: GATA4 Ubiquitinated by CRL4B complex to stimulated Lysosome and promote Ovarian cancer EMT process [RNA-seq]

summary: GATA4 has emerged as a prominent transcription active factor for cardiomyogenesis and carcinogenesis. Ovarian cancer is a lethal cancer for women due to the hard diagnosis and easy metastasis. However, the role of GATA4 in breast cancer metastasis remains poorly understood. Here, we indicated that GATA4 was decreased in ovarian cancer and associated with excessive lysosome function and epithelial-mesenchymal transition (EMT). Mechanically, GATA4 was ubiquitinated by CUL4B, a submit of Cullin-Ring E3 ligase (CRL) complexes, and decreased the histone H3K27 acetylation. In vivo, knock down GATA4 was facilitated the proliferation and metastasis of SKOV3. Genome-wide analysis of the transcriptional target of the GATA4 and GATA4/CUL4B complex identified a cohort of genes including TRM22 and KLK15 that are potential involved in lysosome and EMT. These results suggest that GATA4 as a tumor suppressor to impair the lysosome acid environment and promote ovarian cancer metastasis in vivo and vitro through ubiquitin degradation system initiated by CRL4B complex. Our study supporting the tumor suppression role of GATA4, implied the pursuit of GATA4 as a therapeutic target for cancer intervention.

overall_design: To investagate the function of GATA4 in regulation of ovarian cancer, we overexpression GATA4 in ovaria cancer cell line SOKV3 and find the potential key differential genes and signaling pathway


title: Investigation of transcriptomic signatures associated with sepsis risk in patients with infection

city: Budapest

first: Zsolt

last: Ronai

address: Ulloi u. 26.

department: Molecular Biology

country: Hungary

institute: Semmelweis University

type: Non-coding RNA profiling by high throughput sequencing

summary: Sufficient immune response is responsible for eradicating pathogens and reestablishing tissue homeostasis. However, in certain patients, immune processes become dysregulated, leading to systemic inflammatory response syndrome (SIRS), which often results in life-threatening organ dysfunction. The phenomenon of outgrowing septic shock is associated with a mortality rate of up to 70–80%. The objective of the present data set is to facilitate the identification of transcriptomic signatures associated with the development of sepsis in patients with infection. A total of six patients were included in the study, with blood samples collected at various stages of the disease, ranging from severe septic conditions to periods of temporary improvement and recovery. Following RNA isolation, the mRNA and microRNA levels were determined by NGS. The dataset’s significance stems from the fact that more samples of the same patient were analyzed, ensuring that any observed alteration in the transcription levels is related to the change in medical condition.

overall_design: RNA-seq profiling (including mRNA and miRNA) of blood sample sets of patients with infection at the stage of severe sepsis, at temporary improvement and recovery.

first: Krisztina

last: Molnár

first: Katalin

last: Maricza

first: Zsuzsanna

last: Elek

first: Réka

last: Kovács-Nagy

first: Zsófia

last: Bánlaki

first: Eszter

last: Losoncz

first: Zoltán

last: Fülep

first: János

last: Kádas

first: Gergely

last: Keszler

last: Rónai