title: A comprehensive molecular atlas of the mesenchymal cell types in the mouse liver

city: Huddinge

first: Lars

last: Muhl

address: Blickagången 6

department: MedH

country: Sweden

institute: Karolinska Institutet

summary: The liver plays a crucial role in essential physiological processes, and its impaired function due to liver fibrosis from various causes is an increasingly significant health issue. The liver's functionality relies on the precise arrangement of its cellular structures, yet the molecular architecture of these units remains only partially understood. We created a comprehensive molecular atlas detailing all the major cell types present in the adult mouse liver through deep single-cell RNA sequencing. Our analysis offers new insights into hepatic endothelial and mesenchymal cells, specifically highlighting the differences between the cells of the periportal microvasculature, the sinusoids, and the portal vein, the latter exhibiting a mixed arterio-venous phenotype. We identified distinct subpopulations of hepatic stellate cells, fibroblasts, and vascular mural cells located in different anatomical regions. Comparisons with transcriptomic data from disease models indicate that a previously unrecognized capsular population of hepatic stellate cells expands in response to fibrotic disease. Our findings reveal that various fibroblast subpopulations respond differently to pathological insults. This data resource will be invaluable for advancing therapeutic interventions targeting hepatic diseases.

overall_design: Single-cell transcriptomes were generated from individual FACS-sorted cells captured from the liver of adult, healthy male and female mice by single-cell RNA-sequencing (Smart-seq2).

first: Riikka

last: Pietilä

first: Guillem

last: Genové

first: Giuseppe

last: Mocci

first: Yuyang

last: Miao

first: Jianping

last: Liu

first: Stefanos

last: Leptidis

first: Francesca

last: Del Gaudio

first: Martin

last: Uhrbom

first: Elisa

last: Vázquez-Liébanas

first: Sonja

last: Gustafsson

first: Byambajav

last: Buyandelger

first: Elisabeth

last: Raschperger

first: Johan

last: Björkegren

first: Emil

last: Hansson

first: Konstantin

last: Gaengel

first: Maarja

last: Andaloussi Mäe

first: Marie

last: Jeansson

last: Vanlandewijck

first: Liqun

last: He

first: Carina

last: Strell

first: Xioa-Rong

last: Peng

first: Urban

last: Lendahl

first: Christer

last: Betsholtz


title: The p400 complex promotes HIV-1 latency by suppressing 1 viral transcription and altering the host cell state [RNA-seq]

status: Public on Aug 19 2025

city: Jupiter

first: Susana

middle: T

last: Valente

state: FL

address: 130 Scripps Way

department: Immunology and Microbiology

country: USA

institute: The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology

type: Expression profiling by high throughput sequencing

summary: Eradicating HIV-1 is complicated by latently infected CD4+T cells harboring repressed HIV-1 proviruses that can reactivate. Using a pooled shRNAmir screen of all human chromatin regulators we identified previously unappreciated factors that govern HIV-1 latency and reactivation. Depletion of EP400 and DMAP1, core subunits of the multifunctional p400 complex, strongly derepressed HIV-1 transcription in Jurkat and primary CD4+T cells. EP400/DMAP1 co-localize with paused RNA Polymerase II (RNAPII) at the transcriptional start sites (TSS) of protein-coding genes, limiting RNAPII pause release, with HIV-1 elongation particularly affected. TNF-⍺ stimulation robustly promotes co-recruitment of RNAPII, EP400, and DMAP1 across the HIV-1 genome, which is distinct from other genes where this co-recruitment occurs mainly at the TSS. Depletion of EP400/DMAP1 reactivated HIV transcription independently of histone variant exchange and KAT5 activity, and increased gene expression of key T cell factors known to trans-activate HIV-1. Thus, the p400 complex is a host restriction factor that blocks RNAPII transcriptional elongation at the HIV-1 locus and creates a CD4+T cell state unfavorable for HIV-1 transcription.

overall_design: J-Lat 10.6 cells, wild-type Jurkat cells and primary CD4+ T cells were transduced with shRNAmirs (two independent shRNAmirs as replicates) targeting negative control genes CD8B and CD19 or experimental targets EP400 and DMAP1. For J-Lat 10.6 and WT uninfected Jurkats, RNA-sequencing was performed on transduced cells at 9 days post-transduction. For the primary CD4+ T cell experiment: cells were transduced with shRNAmirs and infected or not with HIVGKO. 9 days later transduced cells that were either uninfected, latently infected or productively infected were FACS purified and RNA-seq was performed. Comparisons were made between EP400/DMAP1 depletion and control shRNAmirs.

first: Luisa

middle: P

last: Mori

first: Chuan

last: Li


title: Myocardial Reprogramming by HMGN1 Underlies Heart Defects in Trisomy 21

status: Public on Aug 25 2025

city: San Francisco

first: Angelo

last: Pelonero

state: CA

address: 1650 Owens Street

department: Cardiovascular Disease Institute

institute: Gladstone Institutes (UCSF)

type: Genome binding/occupancy profiling by high throughput sequencing

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: H3K4me3 profiling of Kdm1a/Kdm5c double-inducible forebrain-specific knockouts

status: Public on Aug 22 2025

city: San Juan de Alicante

first: Sergio

last: Niñerola

state: Alicante

address: Avenida Santiago Ramon y Cajal, s/n

department: Molecular Neurobiology and Neuropathology

country: Spain

institute: CSIC-Instituto de Neurociencias de Alicante

summary: Loss or reduced expression of lysine demethylases (KDMs) is linked to neurodevelopmental disorders and intellectual disability. Given the phenotypic similarities between KDM1A and KDM5C deficient mice, and the convergence of both enzymes in maintaining a repressive state via H3K4 demethylation, we examined their functional interaction using double-inducible, forebrain-specific knockouts (dKDM-ifKOs). These mice showed transcriptional and epigenetic dysregulation beyond the additive effects of individual knockouts, including stronger ectopic expression of non-neuronal genes in hippocampal neurons. Thousands of de novo H3K4me3-enriched regions emerged, indicating synergistic disruption of chromatin regulation. In line with these molecular changes, dKDM-ifKOs displayed more severe behavioral impairments than the single ifKOs, along with altered hippocampal expression of ion channels and increased excitability of CA1 pyramidal neurons. These findings underscore the joint role of ID-linked KDMs in regulating cell-type-specific gene silencing and H3K4 methylation levels to safeguard neuronal identity and responsiveness, as well as cognitive function

overall_design: Kdm1af/f, Kdm5cf/f and CamKIIα-CreERT2 mouse strains have been previously described , they are available at public repositories (Jackson Lab stock #23969; MMRRC stock 066789-UCD; and EMMA EM:02125, respectively). Mice were maintained on a C57BL/6J genetic background. The recombinant protein CreERT2 is dependent on tamoxifen (TMX) administration, and its expression is restricted to principal neurons of the forebrain, where CamKIIα is expressed. CaMKIIα–driven, TMX induced Cre recombination results in the elimination of exons 5 and 6 in Kdm1af/f and exons 11 and 12 in Kdm5cf/f . Mice were 2 to 3-month-old at the time of TMX administration.

first: Niñerola

last: Sergio

first: Paraiso-Luna

last: Juan

first: Barco

last: Angel


title: Regulation of NK effector function by ACLY-generated acetylation [RNA-Seq]

status: Public on Aug 18 2025

city: SAINT LOUIS

first: Megan

last: Cooper

state: MISSOURI

address: MPRB, 6th floor, 4905 Childrens Place

department: Pediatrics

institute: Washington University in St Louis

summary: Natural Killer (NK) cells, integral to viral immunity and tumor clearance, are impacted by metabolism. A prior study revealed that cytokine stimulation boosts the citrate-malate shuttle and cytosolic acetyl-CoA through ATP citrate lyase (ACLY) in NK cells. Acetyl-CoA is vital for fatty acid synthesis and protein acetylation, including histones. To explore the role of ACLY in NK cell function, we generated an inducible NK-specific Acly knockout mouse model. ACLY loss in NKp46+ NK cells did not alter maturation or IFN-γ production in naïve NK cells. However, ACLY-deficient NK cells exhibited notable proliferation defects in IL-15-priming conditions, associated with impaired glycolysis. The stimulation and priming of NK cells through IL-15 is an important mechanism for enhancing effector and anti-tumor functions. Additionally, IL-15-primed ACLY-deficient NK cells showed reduced effector function in response to DAP12-associated activating receptors (NKG2D, Ly49H). This is because ACLY-deficient NK cells produce lower level of DAP12 during IL-15 priming, which was regulated in epigenetic level. These ACLY-driven deficiency was mostly rescued by acetate-generated acetyl-CoA, except glycolysis. Overall, these findings underscore ACLY's importance in NK cell proliferation and DAP12-driven effector functions.

overall_design: RNAseq profiling of sorted YFP+ cells from tamoxifen-treated WT and ACLY KO mice. RNA was extracted on fresh NK, high-dose (hd) IL-15 primed NK and IL-15 primed + NKG2D stimulated NK cells.

first: Hyogon

last: Sohn

first: Ana

last: L. Kolicheski

last: A. Cooper


title: Regulation of NK effector function by ACLY-generated acetylation [CUT&Tag]

overall_design: CUT&Tag of H3K27ac, H3K9ac, H3K27me3 in primed YFP+ NK cells from WT and ACLY KO mice.

first: Yongjun

last: Wang


title: Regulation of NK effector function by ACLY-generated acetylation


title: Cancer-cell-secreted miR-33a remodels extracellular matrix by targeting polyamine metabolism in stroma to promote tumorigenesis

city: wuhan

first: Wei

last: Yan

state: Hubei

address: Bayi Street 229 in Wuchang district

department: College of life science

country: China

institute: Wuhan University

type: Non-coding RNA profiling by high throughput sequencing

summary: Tumor progression depends on the bidirectional interactions between cancer and stroma in the heterogenous tumor microenvironment (TME) partially through extracellular vesicles (EVs). However, the secretary mechanism and biological effect of cancer cell derived EVs on tumor survival under starvation is poorly defined. Here, we identify cancer cells preferentially secrete miR-33a in the tumor core region with poor nutrient level. Exosomal miR-33a suppresses putrescine biosynthesis by targeting AGMAT in stromal cells, where putrescine suppresses the expression of demethylase KDM5C. Chromatin immunoprecipitation sequencing identifies miR-33a/KDM5C axis tightly regulates TIA1 gene, functioning stress granule (SG) marker. Exosomal miR-33a diminishes the assembly of stromal SGs but inducing more extracellular matrix accumulation. Collectively, our study reveals tumor selectively secretes miR-33a through EVs to remodel the stromal SG formation and extracellular matrix profiles to gain survival possibility for cancer cells under starvation, highlighting a novel regulatory mechanism of nutrient level on EV secretion and the function of polyamine metabolism in reshaping epigenetic profiles of TME.

overall_design: Comparative miRNA expression profiling analysis of small RNA deep data sequencing for exosomes

first: Sheng

last: Hu


title: SMAD1/5-Mediated Recruitment of the Histone Demethylase KDM1A Controls Cell Fate Programs in Embryonic Stem Cells [scRNA-seq]

status: Public on Aug 15 2025

city: Tokyo

first: Masato

last: Morikawa

address: 2-21-1 Kaga, Itabashi-ku

department: Advanced Comprehensive Research Organization

country: Japan

institute: Teikyo University

summary: Bone morphogenetic proteins (BMPs) play diverse roles in mouse embryonic stem cell (mESC) biology. Recent studies suggest that BMPs induce multiple cell fates and enhance mESC heterogeneity by cross-activating multiple signaling pathways. Although BMPs primarily signal through SMAD1 and SMAD5 in mESCs, their roles remain incompletely defined. Here, we investigated the SMAD signaling pathway using Smad1/5 double knockout (S1/5 dKO) mESCs. While SMAD1/5 depletion may influence mESC heterogeneity, single-cell RNA sequencing (scRNA-seq) revealed only minor differences between S1/5 dKO and WT cells, suggesting that the observed changes are not because of altered cell states. Chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that SMAD1/5 recruit the histone demethylase KDM1A/LSD1 to specific genomic regions, where it removes H3K4me1/2 marks associated with enhancers. Published scRNA-seq data from Kdm1a-deficient mESCs during embryoid body differentiation further supported this mechanism. This study reveals a transcriptional repression mechanism of SMAD1/5, involving KDM1A-dependent H3K4me1/2 depletion and the regulation of cell type–specific gene expression programs.

overall_design: scRNA-seq: parental E14 mouse ESCs (WT) and Smad1/5 double knockout cells (S1/5 dKO) were submitted for single cell RNA sequencing using the 10x Genomics platform. The experiments were performed without replicates.

first: Daizo

last: Koinuma

first: Kohei

last: Miyazono


title: Campylobacter hepaticus transcriptomics revealed the genes involved in the Spotty Liver Disease (SLD)  pathogenesis

city: Gainesville

first: Subhashinie

last: Kariyawasam

state: Florida

address: 1945 SW 16th Ave

department: Comparative, Diagnostic, and Population Medicine

institute: University of Florida

summary: Campylobacter hepaticus, the causative agent of spotty liver disease (SLD) in commercial layer hens, leads to liver necrosis, reduced egg production, and increased mortality. Despite its impact, the pathogen’s virulence mechanisms remain poorly understood. This study used high-throughput transcriptomics to analyze gene expression profiles of C. hepaticus cultured in vitro bile, infected with LMH cells, and SLD affected chicken livers (in vivo) obtained from field cases to uncover key factors involved in host adaptation and pathogenicity

overall_design: To investigate the differential gene expression profiles of C. hepaticus in three distinct conditions (bile, LMH cell line, and SLD infected- liver)

first: Varsha

last: Bommineni

first: Lekshmi

middle: K

last: Edison

first: Chaitanya

last: Gottapu

first: Gary

middle: D

last: Butcher


title: A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (Multiome scRNA-seq/scATAC-seq)

city: Vienna

first: Florian

last: Halbritter

address: Zimmermannplatz 10

country: Austria

institute: St. Anna Children's Cancer Research Institute (CCRI)

summary: CBFA2T3::GLIS2 (CG) is an oncogenic fusion protein found in high-risk pediatric acute megakaryoblastic leukemia (AMKL). To gain insight into its leukemogenic mechanism, we developed a disease model based on genetically modified human induced pluripotent stem cells. We found that CG expression disrupts myeloid differentiation in this model via two alternate paths: either by delaying differentiation of aberrant megakaryocytes (aMK) or by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state akin to AMKL tumor cells. We characterized the gene-regulatory networks characterizing both cell states by single-cell and epigenome analysis, and observed that CG sustains aMKPs along with cooperators GATA2 and ERG, while repressing differentiation factors like CEBPA, LYL1, and NFE2. In contrast, aMKs maintained many differentiation factors and did not up-regulate regulators of self-renewal. In future, our findings may contribute to improved diagnostic and therapeutic procedures aimed at interconverting cell states in CG-positive patients.

overall_design:
We established a new hiPSC lines harboring an endogenous conditional CG allele and equipped with a degradation tag.  We generated gene expression (RNA-seq, scRNA-seq), chromatin (ChIP-seq, ATAC-seq), and multimodal (scRNA-seq+scATAC-seq) profilings in longitudinal fashion (early = Day 12-13, intermediate = Day 22-25, longterm = Day 72-115 ) for a comprehensive benchmark and characterization of our model.
Please note that CellRanger did not yield any outputs for the RNA-seq modality of the 'CG_DTAG13_D25_REP1 + CG_DTAG13_D25_REP2 + CG_DTAG13_D25_REP3 GEX' sample.

first: Mohamed

middle: R

last: Shoeb

first: Dagmar

last: Schinnerl

first: Lisa

middle: E

last: Shaw

first: Matthias

last: Farlik

first: Sabine

last: Strehl

first: Klaus

last: Fortschegger


title: Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics

status: Public on Aug 14 2025

city: Geneva

first: Vasilis

last: Dionellis

address: 30, quai Ernest-Ansermet

country: Switzerland

institute: University of Geneva

summary: Cyclin-dependent kinases (CDKs) coordinate DNA replication and cell division, and play key roles in tissue homeostasis, genome stability and cancer development. The first step in replication is origin licensing, when minichromosome maintenance (MCM) helicases are loaded onto DNA by CDC6, CDT1 and the origin recognition complex (ORC). In yeast, origin licensing starts when CDK activity plummets in G1 phase, reinforcing the view that CDKs inhibit licensing. Here we show that, in human cells, CDK4/6 activity promotes origin licensing. By combining rapid protein degradation and time-resolved EdU-sequencing, we find that CDK4/6 activity acts epistatically to CDC6 and CDT1 in G1 phase and counteracts RB pocket proteins to promote origin licensing. Therapeutic CDK4/6 inhibitors block MCM and ORC6 loading, which we exploit to trigger mitosis with unreplicated DNA in p53-deficient cells. The CDK4/6-RB axis thus links replication licensing to proliferation, which has implications for human cell fate control and cancer therapy design.

overall_design: EdUseq data of RPE CDC6d CDT1d clone #1 cells under control conditions or after treatment with ADN and/or Palbociclib

first: Anastasia

last: Sosenko Piscitello

first: Ann-Sofie

last: Nillsson

first: Michael

last: Hawgood

first: Abid

middle: H

last: Sayyid

middle: S

first: Sotirios

middle: G

last: Ntallis

first: Pratikiran

last: Bajgain

first: Jiri

last: Bartek

first: Thanos

last: Halazonetis

first: Bennie

last: Lemmens


title: SMAD1/5-Mediated Recruitment of the Histone Demethylase KDM1A Controls Cell Fate Programs in Embryonic Stem Cells [ChIP-seq]

first: Masato

last: Morikawa

overall_design: ChIP-seq: profiles of histone marks and transcription factors in parental E14 mouse ESCs (WT) and Smad1/5 double knockout cells (S1/5 dKO) were generated using specific antibodies. The experiments were performed in duplicate.

first: Daizo

last: Koinuma

first: Kohei

last: Miyazono


title: Regulation of Feather Length: FGF/IGF Signaling and NOTCH/YAP Modulation of Progenitor Cell Topology [scRNA-seq]

city: Los Angeles

first: Ping

last: Wu

state: California

address: 2011 Zonal Ave HMR313A

institute: University of Southern California

summary: The regulation of organ size is a fundamental biological question. This study investigates how feather length is regulated in chickens. We found collar bulge stem cell zones vary in size: main sickle > lesser sickle > contour feathers. During growth, IGF and FGF9 signaling are highly expressed, while BMP, WIF1 and FGF18 increase toward growth termination. Functional assays show that IGF/FGF signaling promotes feather elongation via tyrosine kinase receptor signaling. scRNA-seq analysis reveals accelerated differentiation of keratinocytes in short contour feathers compared to long sickle feathers. In Phoenix chickens, superlong main sickle feathers exhibit specialized stem cell zones with enhanced DLL1 expression and expanded intermediate-layer cell clusters with dynamic interactions involving NOTCH1/DLL1, YAP1, and WNT signaling in progenitor zones in the proximal follicle. Perturbation experiments induce short feather phenotypes arrested at various stages, shedding light on versatile regulatory mechanisms and paving the way for functional control of diverse feather lengths.

overall_design: Bulk RNA-seq for 3 stages of feather progenitor zone , single cell RNA-seq for feather follicles from White leghorn chicken and Phoenix chicken

first: Federico

last: Bocci

first: Qing

last: Nie

first: Cheng-Ming

last: Chuong


title: MicroRNA expression in semitendinosus muscle in cattle breeds of varying marbling deposition -  Hereford & Holstein-Freisian vs Limousine cattle

city: Warsaw

first: Tomasz

last: Sadkowski

address: Nowoursynowska 159

department: Department of Physiological Sciences

country: Poland

institute: Warsaw University of Life Sciences - SGGW

summary: The goal was to identify miRNA characteristic for muscle tissue with high content of intramuscular fat (IMF) in semitendinosus muscle derived from bulls characterized by higher amounts of IMF ( Hereford - HER and Holstein-Friesian - HF) in comparison to the bulls characterized by a low content of IMF (Limousin - LIM)

overall_design: Comparison of miRNA expression profiles in semitendinosus muscle of a high content of muscle IMF (HER and HF) vs. low content of IMF (LIM) - used as a control

first: Anna

last: Ciecierska


title: Leaf transcriptome of apple knock-out transgenic lines of MdAGG by CRISPR/Cas9 strategy

status: Public on Aug 12 2025

city: Beaucouzé

first: Matthieu

last: Gaucher

address: 42 rue Georges Morel

department: SPE

country: France

institute: INRAE

summary: Investigation of whole genome gene expression level changes in Acibenzolar-S-methyl-treated leaves of three MdAGG-knock-out transgenic lines (mdagg-2, mdagg-3 and mdagg-4) versus treated but non-transformed plants (wild-type)

overall_design: A total of 8 samples, corresponding to 2 biological replicates (bulk of leaves from 2 independent experiments) for each transgenic lines and non-transformed control, were used for differential gene expression analysis. Plants were treated with acibenzolar-S-methyl (ASM) and leaves were collected 3 days post-treatment.

first: Antoine

last: Bodelot

first: Emilie

last: Vergne

first: Axelle

last: Frantz

first: Alexandre

last: Degrave


title: Multidimensional Deep Receptor Scanning Reveals Constraints on GPCR Biosynthesis [RNA-seq]

city: Lafayette

first: Austin

last: Tedman

state: IN

address: 716 Brown St Apt 4

department: Chemistry

institute: Purdue University

summary: G protein-coupled receptors (GPCRs) mediate a variety of signaling pathways and are among the most common pharmacological targets. While advances in structural biochemistry have provided deep functional insights into dozens of key receptors, many of the 800+ human GPCRs remain understudied. In the following, we introduce a versatile “deep receptor scanning” platform that can be used to experimentally characterize 767 human GPCRs and 174 known GPCR splice variants in parallel. We quantitatively characterize the relative abundance of receptor transcripts, their translational efficiency, and the plasma membrane expression of each receptor in the context of a recombinant pool of HEK293T cells expressing individual GPCRs. We then employ machine learning to identify specific structural features that modulate GPCR expression. This experimental platform and informatic approach are compatible with a variety of assays and can be used to efficiently explore the biochemical and pharmacological properties of the GPCRome.

overall_design: Total RNA-seq of both mock and stably transfected HEK 293T cells where each cell encodes one of 767 single stably expressed GPCRs


title: The p400 complex promotes HIV-1 latency by suppressing 1 viral transcription and altering the host cell state [ChIP-seq]

first: Susana

last: Valente

overall_design: J-Lat 10.6 cells were transduced with shRNAs targeting CD8B (negative control), EP400 or DMAP1. Following 2 days of puromycin selection and 7 days expansion of cells, cells were collected for native ChIP-seq.

first: Luisa

last: Mori

first: Chuan

last: Li


title: Targeting CyclinD1-CDK6 to Mitigate Senescence-Driven Inflammation and Age Associated Functional Decline

status: Public on Aug 13 2025

city: La Jolla

first: K. Garrett

last: Evensen

address: 10010 N Torrey Pines Rd

institute: The Salk Institute for Biological Studies

summary: Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the Senescence Associated Secretory Phenotype (SASP) and interferon-stimulated genes (ISGs). Cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated in these non-proliferating cells. We show that CCND1 and its kinase partner CDK6 drive SASP and ISG expression in senescent cells by promoting DNA damage accumulation. This leads to the formation of cytoplasmic chromatin fragments (CCFs) that activate pro-inflammatory CGAS-STING signaling. The tumor suppressor p53 (TP53) and its target p21 (CDKN2A) antagonize this CCND1-CDK6–dependent DNA damage accumulation pathway to suppress the SASP. In aged mouse livers, senescent hepatocytes show increased Ccnd1 expression. Hepatocyte-specific Ccnd1 knockout or treatment with the Cdk4/6 inhibitor Palbociclib reduces DNA damage and ISGs in aged mouse liver. Notably, Palbociclib also suppresses frailty and improves physical performance of aged mice. These findings reveal a novel role for CCND1/CDK6 in regulating DNA damage and inflammation in senescence and aging, highlighting it as a promising therapeutic target.

overall_design: In this study, we collected CosMx spatial transcriptomics data on young, old, and Pten KO mice using the 1,000 plex panel

first: Adarsh

last: Rajesh

first: Peter

last: Adams

first: K

last: Garrett Evensen


title: Phosphorylation of CSDE1 drives ribosome interactions with implications for cancer malignancy

city: Barcelona

first: Neus

last: Mestre-Farràs

state: Barcelona

address: C/ Doctor AIguader 88

institute: CRG

summary: The RNA-binding protein CSDE1 is a key regulator of mRNA stability and translation in a broad spectrum of biological processes. We have previously shown that CSDE1 functions as an oncoprotein in melanoma, where it promotes invasion and metastasis, whereas it behaves as a tumour suppressor in squamous cell carcinoma, a tumor derived from keratinocytes. The reasons underlying these context-specific behaviours are unknown. To identify melanoma-specific vulnerabilities, we have compared CSDE1 protein isoforms and post-translational modifications in melanoma cells and keratinocytes, as well as in cells of different tumorigenic potential. Combining Nanopore sequencing with two-dimensional gel electrophoresis and proteomics, we identify one major CSDE1 isoform expressed in melanoma cells and patient samples and find that CSDE1 phosphorylation and interactions with ribosomes represent an early event in cellular transformation, correlating with changes in the subcellular localization of CSDE1. Our data show that CSDE1 phosphorylation promotes de novo interactions of CSDE1 with ribosomes, uncovering a specific vulnerability of melanoma cells that might be harnessed for therapeutic intervention.

overall_design: Nanopore direct cDNA sequencing of human SKMel-147 cells and primary mouse immortalized keratinocytes (PMK) in duplicates.

first: Ivan

last: Milenkovic

first: Annagiulia

last: Ciocia

first: Rebeca

last: Medina

first: Eva Maria

last: Novoa

first: Fátima

last: Gebauer


title: Tissue-specific immunosuppressive and proliferating macrophages fuel early metastatic progression of human colorectal cancer to liver

status: Public on Aug 11 2025

city: Rozzano, Milan

first: Paolo

last: Marzano

address: Via Alessandro Manzoni 56

country: Italy

institute: Humanitas Research Hospital

summary: Early synchronous colorectal liver metastasis (CRLM) represents a clinical condition characterized by the simultaneous presence of primary colorectal cancer (CRC) and metastatic liver lesions (CRLM). The present study characterizes the tissues-specific transcriptomes, phenotypes, and functional relevance of tumor associated macrophages (TAMs) within the tumor microenvironment (TME) of CRC and CRLM specimens in patients who underwent simultaneous surgical removals of these malignancies. The high-throughput single-cell transcriptional analysis revealed an inverse ratio of inflammatory and immunoregulatory TAMs in CRC and CRLM TMEs, along with significant heterogeneity in both tumoral tissues. Importantly, we found that inflammatory TAMs in CRC express inhibitory ligands that might support the tumor immune escape, thus favoring liver metastatic progression. In contrast, CRLM lesions possess a highly immunosuppressive milieu characterized by large proliferative CTLA4pos immunoregulatory TAMs and by the presence of IL7Rpos cytotoxic TAMs. Higher frequencies of these specific TAM subsets in CRLM are associated with a shorter disease-free survival and worse patient prognosis. The identification and characterization of immunoregulatory TAMs preferentially enriched in CRLM is key for the development of novel immune-therapeutic strategies aimed at boosting anti-cancer immune responses within TME.

overall_design: Single-cell RNA sequencing (scRNA-seq) was performed on samples collected from three synchronous colorectal-liver metastasis patients who underwent simultaneous surgical resection of the primary tumor and liver metastasis. For each patient, matched samples were obtained from core-tumor adjacent tissue regions (peritumor) of the colon (n = 3) and liver (n = 3), as well as from peripheral blood (n = 2). scRNA-seq was performed on FACS-sorted viable/CD45+ immune-enriched populations in the colon and liver, and on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood.

first: Cristiana

last: Soldani

first: Valentina

last: Cazzetta

first: Barbara

last: Franceschini

first: Sara

last: Terzoli

first: Anna

last: Carletti

first: Michela

middle: A

last: Polidoro

first: Federica

last: Marchesi

first: Massimo

last: Locati

first: Gianluca

last: Basso

first: Ana

last: Lleo

first: Guido

last: Costa

last: Torzilli

first: Flavio

last: Milana

first: Rocco

last: Piazza

first: Paola

last: Spaggiari

first: Luca

last: Di Tommaso

first: Joanna

last: Mikulak

first: Domenico

last: Mavilio

first: Matteo

last: Donadon


title: Early-life gut microbiome maturity regulates blood-brain barrier and cognitive development

city: Chicago

first: Jing

last: Lu

state: Illinois

address: 900 E 57th St

institute: University of Chicago

summary: The gut microbiome is an emerging factor in the neurobiology of disease. Blood-brain barrier (BBB) integrity is essential for proper brain function. However, the role the initial microbiome plays in BBB and brain development is unclear. In this study, we colonized germ-free pregnant mice with human full-term- or preterm-infant-derived gut microbiota, thereby establishing these communities in the resulting offspring. We discovered that mice harboring a full-term-associated microbiome exhibited stronger memory and learning capabilities and dramatically decreased early-life BBB permeability when compared to those with a prematurity-associated microbiome. Whole-brain single-cell RNA sequencing revealed downregulation of synaptic signaling genes in BBB cell types of mice with the prematurity-associated microbiome, indicating that microbiome maturity influences BBB transcriptional programs that support cognitive development. Comprehensive metagenomics and metabolomics uncovered bacterial populations and genomic pathways corresponding with decreased levels of circulating long-chain acylcarnitines and lysophosphatidylcholines in mice with the full-term-associated microbiome. Our findings highlight the microbiome as a therapeutic target for improving long-term neurodevelopmental outcomes due to its effect on the early-life BBB.

overall_design: We transplanted germ-free, pregnant C57BL/6J mice with human full-term- or preterm-infant-derived gut microbiota, which established these communities in the resulting offspring. We studied the neurodevelopment of these offspring, focusing on the blood-brain barrier. We performed whole-brain scRNA-seq in mice at two weeks postnatal.

first: Zachary

middle: M

last: Zemmel

first: Xiaobing

last: Fan

first: Yueyue

last: Yu

first: Erica

last: Markiewicz

first: Hsiu-Ming

last: Tsai

first: Lei

first: Jessica

middle: C

last: Little

first: Ramanujam

last: Ramaswamy

first: Bree

last: Andrews

first: Erika

last: Claud


title: Primary murine high-grade glioma cells derived from RCAS/tv-a diffuse glioma model reprogram naïve T cells into immunosuppressive regulatory T lymphocytes.

city: Columbus

first: Alessandro

last: Canella

state: OH

address: 700 Children’s Drive

department: Institute for Genomic Medicine

institute: Nationwide Children's Hospital

summary: High-grade gliomas (HGG) and glioblastomas (GBM) are the most aggressive and lethal brain tumors. The standard of care (SOC) currently includes gross safe surgical resection followed by chemoradiotherapy. The main chemotherapeutic agents are the DNA alkylating agent Temozolomide (TMZ) and adjuvants. Due to the outdated therapeutic protocols and lack of specific treatments, there is an urgent and rising need to improve our understanding on the tumor biology and to design more effective therapeutic strategies. In vitro models are essential for investigating glioma biology and testing novel therapeutic approaches. While the use of commercially available and patient-derived glioma cell lines for in vitro studies is a common practice, they exhibit several limitations including failing to maintain genetic and phenotypic diversity of primary tumors, going through genetic drift over time, and often lacking the invasive and stem-like characteristics of patient tumors. These limitations can lead to inconsistent and non-reproducible results, hampering translational research progress. In this study, we established a novel primary murine high-grade glioma cell line, isolated from an immunocompetent HGG-bearing RCAS/t-va mouse. We characterized the transcriptome and phenotype to ensure this cell line resembles the nature of high-grade gliomas and retains the ability to reprogram primary murine T lymphocytes.

overall_design: RNA was extracted from #4 CT2A and #4 BRCAS1 cell lines after 4 days of cell culturing, and wih less than 8 passages. Samples were processed for total RNAseq

first: Mykyta

last: Artomov

first: Aleksandr

last: Ukhatov

first: Sakthi

last: Rajendran

first: Phillip

last: Perez

first: Uksha

last: Saini

first: Jack

last: Hedberg

first: Kevin

last: Cassady

first: Prajwal

last: Rajappa


title: Induction of embryonic axes by distinct population of the Hensens's node [scRNA_HH6_TrunkGraft]

city: Boston

first: Marcos

last: Simoes-Costa

state: Massachusetts

address: 300 Longwood Ave

department: Pathology

institute: Boston Children's Hospital

summary: The vertebrate body plan is established during gastrulation through the activity of the organizer, a specialized group of cells that harbors the ability to instruct fate and morphogenesis in the early embryo. In Xenopus, the organizer is segregated into head and trunk subpopulations, which promote the patterning of the embryonic antero-posterior axis. Here we profiled the avian organizer populations located in the Hensen’s node using single-cell RNA-seq. Our results reveal that the chick organizer is composed of two distinct populations expressing factors known to regulate the formation of head structures and posterior mesoderm. Mapping of trajectory analysis and RNA-velocity of the Hensen’s node in different embryonic stages indicate that the segregation into head and trunk subpopulations occurs at late gastrula stage HH4. The trunk population induces the formation of notochord and somites when ectopically grafted into a host embryo.

overall_design: Examination of transcriptome of single cells from chick embryonic tissue grafted with HH6 Hensen's node

first: Tatiane

last: Kanno


title: Hepatitis C virus NS3 helicase contributes to (-) strand RNA synthesis

city: Würzburg

first: Alexander

last: Gabel

address: Josef-Schneider-Str. 2 / D15

country: Germany

institute: Helmholtz Institute for RNA-based Infection Research

summary: Many positive strand RNA viruses encode helicases, but their distinct functions in viral replication cycles is poorly understood. Here, we identify a mutation in the helicase domain of HCV non-structural protein 3 (NS3h), D1467G, which specifically affects (-) strand synthesis, phenocopying mutations in the 3' untranslated region of the genome. D1467G does not impair helicase activity in vitro or the binding of NS3h to critical cis-acting RNA elements, but reduces the interaction of NS3h and NS5B polymerase, potentially contributing to defective (-) strand synthesis. AlphaFold predictions of complexes between NS3h, RNA and/or NS5B suggest that NS3h both remodels the cis-acting RNA elements and unwinds the terminal stem-loop of the HCV genome rendering the template accessible for de novo initiation of (-) strand synthesis by NS5B. Overall, our study provides evidence for a defined function of a viral helicase in (-) strand genome synthesis of a positive strand RNA virus.

sample_organism:
Homo sapiens
Hepacivirus hominis

platform_organism:
Homo sapiens
Hepacivirus hominis

overall_design: Characterization of protein-RNA interaction sites using enhanced crosslinking and immunoprecipitation (eCLIP) in combination with RNA-sequencing.

first: Philipp

last: Ralfs

first: Stéphane

last: Bressanelli

first: Lina

last: Günter

first: Paul

last: Rothhaar

first: Kyle

middle: J

last: Price

first: Thibault

last: Tubiana

first: Mathias

last: Munschauer

first: David

last: Frick

first: Volker

last: Lohmann


title: Induction of embryonic axes by distinct population of the Hensens's node [scRNAseq]

overall_design: Examination of transcriptome of single cells from chick embryos at stages HH3, HH4 and HH6


title: Induction of embryonic axes by distinct population of the Hensens's node

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

overall_design: Refer to individual Series


title: Prenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities

status: Public on Aug 10 2025

city: Rehovot

first: Alon

last: Chen

address: Herzl 234

country: Israel

institute: The Weizmann Institute of Sciencee

summary: Prenatal stress (PNS) is a well-established risk factor for psychiatric disorders, yet the underlying neurobiological mechanisms remain unclear. Here, we demonstrate that PNS induces long-term behavioral abnormalities, including increased anxiety- and depressive-like behaviors in adult male mice. To investigate potential neurodevelopmental disruptions, we analyzed the medial prefrontal cortex (mPFC) at key postnatal stages. RNA sequencing at postnatal day 1 (P1) revealed significant transcriptional changes, particularly in genes associated with neuronal migration and differentiation, with a diminished effect by P14. Histological analysis identified a transient imbalance in inhibitory neuron subpopulations, PNS decreased the density of early-born MGE-derived neurons while increasing late-born CGE-derived neurons at P1. EdU labeling confirmed that these shifts were time- and subtype-specific, affecting inhibitory neuron proliferation at distinct embryonic stages. By P15, these neuroanatomical alterations largely resolved, yet behavioral abnormalities persisted into adulthood. Our findings suggest that PNS disrupts inhibitory neuron development during a critical early window, leading to lasting behavioral consequences despite the transient nature of anatomical changes. This study highlights the selective vulnerability of inhibitory neuron subtypes to early-life stress and provides insight into potential mechanisms underlying stress-related psychiatric disorders.

overall_design: Pregnant dams were exposed to prenatal stress or used as control,  brains of the offspring were collected at either one day postnatally (P1) or at two weeks of age (P14). Bulk RNA was preformed on dissected mPFC. A total of four samples were used for each condition and each timepoint.

first: Keren

last: Shoshani-Haye

first: Gilgi

last: Friedlander


title: Single nuclei RNA-seq of Ossabaw pig atherosclerotic and healthy aortae

city: Leipzig

first: Olga

last: Bondareva

state: Saxony

address: Philipp-Rosenthal-Straße 27

department: HI-MAG

institute: Helmholtz Zentrum München

summary: Atherosclerosis is a major contributor to cardiovascular diseases. Well-established preclinical models that can accurately recapitulate human atherosclerosis development and progression are necessary for developing new therapeutics. Pig models are extensively used in cardiovascular research due to their physiological similarities to humans. However, their translational efficacy into clinical settings has remained limited. To ensure better translational outcomes, a deeper molecular characterization of atherosclerotic disease mechanisms in swine models is urgently required. Methods: To address this gap, we employed single nuclei transcriptomics to characterize healthy and atherosclerotic aortas in the Ossabaw pig model. We analyzed over 36,000 nuclei from aortas of 5 adult male castrated pigs kept on atherogenic and chow diets. In-depth single-nuclei transcriptomic and cell-cell communication analyses were undertaken to uncover molecular changes in swine atherosclerosis development. Comparisons to human and mouse atherosclerosis were used to establish the veracity of the Ossabaw pig in modeling human disease.

overall_design: Castrate male Ossabaw pigs of 12-month age were put on HF/HFru or chow diet for 9 months. Abdominal aortae were dissected and snap-frozen. Frozen tissues were processed for nuclei isolation followed by snRNA-seq protocol. Single nuclei RNA-seq was performed using 10x Next GEM Single Cell 3 GEM kit v3.1 according to the manufacturers protocol. Separate 10x genomics reactions were used for each sample. Generated libraries were sequenced on an Illumina NovaSeq with >27.5 x 10^3 reads per cell followed by de-multiplexing and mapping to the domesticated pig genome (build Sscrofa11) using CellRanger v5.0. Further analyses were performed using Seurat package v.5.0.


title: RNA N-glycosylation enables innate immune evasion and homeostatic efferocytosis

city: Avon

first: Beiyan

last: Zhou

state: Connecticut

address: 263 Farmington Ave, Immunology

department: Immunology

institute: UCONN Health

summary: Glycosylation is central to the localization and function of biomolecules1. We recently discovered that small RNAs undergo N-glycosylation2 at the modified RNA base 3-(3-amino-3-carboxypropyl) uridine (acp3U)3. However, the functional significance of N-glycosylation of RNAs is unknown. Here we show that the N-glycans on glycoRNAs prevent innate immune sensing of endogenous small RNAs. We found that de-N-glycosylation of cell culture-derived and circulating human and mouse glycoRNA elicited potent inflammatory responses including the production of type I interferons in a TLR3- and TLR7-dependent manner. Further, we show that N-glycans of cell surface RNAs prevent apoptotic cells from triggering endosomal RNA sensors in efferocytes, thus facilitating the non-inflammatory clearance of dead cells. Mechanistically, N-glycans conceal the hypermodified uracil base acp3U, which we identified as immunostimulatory when exposed in RNA. Consistent with this, genetic deletion of an enzyme (DTWD2) that synthesizes acp3U abrogated innate immune activation by de-N-glycosylated of small RNAs and apoptotic cells. Additionally, synthetic acp3U-containing RNAs are sufficient to trigger innate immune responses. Thus, our study has uncovered a natural mechanism by which N-glycans block RNAs from inducing acp3U-driven innate immune activation, demonstrating how glycoRNAs exist on the cell surface and in the endosomal network without inducing autoinflammatory responses.

overall_design:
THP1 monocytes were differentiated into macrophages with phorbol 12-myristate-13-acetate (PMA) for 24 hours.
THP1-derived macrophages were differentiated via phorbol 12-myristate-13-acetate (PMA) for 24 hours then transfected with either of the following:
1. small RNA harvested from HeLa cells (UntxtRNA)
2. PNGase F-treated small RNA harvested from HeLa cells (PNGaseRNA)
3. Unmodified synthetic 18-mer tRNA fragment (Unmod-tRNA)
4. Acp3U-8C modified synthetic 18-mer tRNA fragment (Acp3U8C-tRNA)
Following 6-hour incubation, RNA was harvested via Zymo Directzol RNA kit.

first: Alyssa

last: Matz

first: Vijay

last: Rathinam

first: Vincent

last: Graziano


title: A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (scRNA-seq)

first: Florian

last: Halbritter

summary: CBFA2T3::GLIS2 (CG) is an oncogenic fusion protein found in high-risk pediatric acute megakaryoblastic leukemia (AMKL). To gain insight into its leukemogenic mechanism, we developed a disease model based on genetically modified human induced pluripotent stem cells. We found that CG expression disrupts myeloid differentiation in this model via two alternate paths: either by delaying differentiation of aberrant megakaryocytes (aMK) or by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state akin to AMKL tumor cells. We characterized the gene-regulatory networks characterizing both cell states by single-cell and epigenome analysis, and observed that CG sustains aMKPs along with cooperators GATA2 and ERG, while repressing differentiation factors like CEBPA, LYL1, and NFE2. In contrast, aMKs maintained many differentiation factors and did not up-regulate regulators of self-renewal. In future, our findings may contribute to improved diagnostic and therapeutic procedures aimed at interconverting cell states in CG-positive patients.

overall_design: We established a new hiPSC lines harboring an endogenous conditional CG allele and equipped with a degradation tag.  We generated gene expression (RNA-seq, scRNA-seq), chromatin (ChIP-seq, ATAC-seq), and multimodal (scRNA-seq+scATAC-seq) profilings in longitudinal fashion (early = Day 12-13, intermediate = Day 22-25, longterm = Day 72-115 ) for a comprehensive benchmark and characterization of our model.

first: Mohamed

last: Shoeb

first: Dagmar

last: Schinnerl

first: Lisa

last: Shaw

first: Matthias

last: Farlik

first: Sabine

last: Strehl

first: Klaus

last: Fortschegger


title: Embryonic exposure to TPhP elicits osteotoxicity via metabolic disruption in Oryzias latipes

status: Public on Aug 08 2025

city: RALEIGH

first: Dereje

last: Jima

state: NC

address: 850 Main Campus Drive

department: CHHE

institute: NCSU

summary: Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post-fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk.

overall_design: Total RNA was extracted from axial tissue derived from DMSO- and TPhP-treated 14 day old medaka larvae as 4 biological replicates of 15-20 pooled larvae.

first: Melissa

last: Gronske

first: Jamie

last: Cochran

first: David

last: Buchwalter

first: Heather

last: Stapleton

first: Seth

last: Kullman


title: Seeding of visceral adipose tissue with perinatally generated regulatory T cells shapes the metabolic tenor in mice

first: CBDM

last: Lab

state: MA

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

institute: Harvard Medical School

summary: The Foxp3+CD4+ regulatory T cells (Tregs) generated around birth are phenotypically and functionally distinct from those engendered during adulthood. That perinatally produced Tregs persist for a protracted period in peripheral lymphoid organs has been well documented, as has their superior ability to protect the organism from many autoimmune diseases. However, their contribution to pools of nonlymphoid-tissue Tregs and their homeostatic  functions therein have been little studied. We show that perinatal Tregs preferentially derive from a CD25+Foxp3- thymocyte progenitor; that they seed and persist to varying degrees in every nonlymphoid tissue examined; and that transient depletion of perinatally generated Tregs in adults, but not in neonates, is followed by poor reconstitution of Treg numbers and phenotypes in epidydimal (e) VAT, the skin and the meninges but not in several lymphoid and other nonlymphoid tissues. Potential clinical implications of such a deficiency are highlighted by findings on mice subjected to weight cycling: imposing a low-fat – high-fat – low-fat diet regimen results in an impoverished eVAT, but not spleen, Treg compartment, accompanied by normal weight gain and glucose tolerance but profound insulin resistance. These findings point to a layered immune system, the different layers exerting specialized, non-redundant functions.

overall_design: Regulatory T cell (Treg) differentiation in the thymus was examined by flow-cytometrically purifying Treg progenitors from male C57B6.Foxp3.GFP perinatal moue thymus based on surface CD25 and FoxP3-GFP expression at day 5, day 12, and day 49 post birth (P1 = CD4+CD8-CD25+FoxP3- progenitors, P2= CD4+CD8-CD25-FoxP3+ progenitors).  To explore why perinatally generated Tregs variably repopulate tissues, 12 week old C57B6.Foxp3.eGFP.DTR+ and DTR- male littermates were i.p. injected with diptheria toxin for three consecutive days to deplete existing Tregs. Mice were rested for 8-9 weeks before analyzing a panel of tissues (Spleen, Lung, Liver, Ear Skin, and Visceral Adipose Tissue). Treg populations in each tissue were digested with a tissue specific protocol and cytometrically purified based on CD4+Foxp3GFP+ expression.  Each replicate consists of 500-1000 double sorted cells following the standard Immgen (www.immgen.org) protocol.

first: Miguel

last: Marin-Rodero

first: Teshika

last: Jayewickreme

first: Diane

last: Mathis


title: Human iPSC-Derived Spinal Neural Progenitors Enhance Sensorimotor Recovery in Spinal Cord-Injured NOD-SCID Mice via Differentiation and Microenvironment Regulation

status: Public on Aug 05 2025

city: Beijing

first: Miao

last: Xu

address: No. 31 Huatuo St., Daxing District, Beijing, P.R.China

institute: National Institutes for Food and Drug Control

summary: We developed a therapeutic approach by transplanting spinal neural progenitor cells (spNPGs), derived from human induced pluripotent stem cell (iPSC)-generated neuromesodermal progenitors, into a contusive spinal cord injury (SCI) model in NOD-SCID mice. Single-cell RNA sequencing mapped the in vitro differentiation of iPSC-spNPGs, confirming their specification into spinal neuronal lineages. Single-nucleus transcriptomics at one-week post-transplantation showed that the grafted cells differentiated in vivo into motor neurons and two interneuron subtypes (V2 and dI4).

overall_design: Human cord blood monocytes derived iPSC was differentiated into spinal neural progenitor cells with posterior identity. Cells were sampled at distinct time points (day-1, 3, 6, 12 and 18) during the in vitro differentiation process and processed for scRNA-seq libraries construction using Singleron GEXSCOPE® protocol (Singleron Biotechnologies, China). After spNPG tranplation into SCI mice. The nuclei of lesion site in the mouse spinal cord were isolated and performed snRNA-seq using the Chromium platform (10X Genomics, USA).

first: Xuanbao

last: Yao

first: Kehua

last: Zhang

first: Tao

first: Jiajie

last: Xi

first: Xiang

last: Li

first: Shufang

last: Meng


title: DNA Methylation Profile in Psoriasis Vulgaris and Generalized Pustular Psoriasis Patients

status: Public on Aug 07 2025

city: Jakarta

first: Ariel

last: Pradipta

state: Jakarta

address: Jl. Salemba Raya No.6

department: Biochemistry and Molecular Biology

country: Indonesia

institute: Faculty of Medicine Universitas Indonesia

type: Methylation profiling by high throughput sequencing

summary:
Epigenetics plays a role in the pathogenesis of psoriasis vulgaris and generalized pustular psoriasis (GPP) through DNA methylation modifications that cause changes in immune responses. Psoriasis vulgaris is dominated by autoimmune responses, driven by Th17 cells producing IL-17, whereas GPP is dominated by autoinflammatory responses resulting from IL-36 dysregulation and neutrophil hyperactivation.
Objective: This study aims to determine the DNA methylation profile and analyze the differences in IL-17 and IL-36 levels in both psoriasis phenotypes and healthy controls.
Method: This study employed a cross-sectional design, comprising 20 patients with psoriasis vulgaris, three patients with GPP, and 13 healthy controls. DNA methylation profiles were assessed using Reduced Representation Methylation Sequencing, while IL-17 and IL-36 levels were assessed using ELISA.
Results: Increased 5-methyl cytosine (5mC) was identified in psoriasis vulgaris and GPP compared to healthy controls. Increased 5mC at the FOXP3 promoter was identified in GPP and psoriasis vulgaris with high IL-17 levels, while decreased 5mC at the CARD14 promoter was identified in psoriasis vulgaris with high IL-17 levels. GPP showed higher IL-17 levels than healthy controls (p<0.05). IL-17 levels in psoriasis vulgaris showed no significant difference compared to GPP and healthy controls (p>0.05). IL-36 levels did not differ significantly among the three groups, with the highest IL-36 levels observed in psoriasis vulgaris (p>0.05).
Conclusion: Increased DNA methylation in the FOXP3 gene promoter is predicted to cause high IL- 17 levels in psoriasis vulgaris and GPP, while IL-36 levels are higher only in psoriasis vulgaris.

overall_design: DNA methylation was analyzed in peripheral blood mononuclear cells (PBMCs) from two patients with psoriasis vulgaris (PV), one patient with generalized pustular psoriasis (GPP), and one healthy control, all without any intervention.

first: Monica

last: Putri

first: Windy

last: Budianti

first: Faris

middle: I

last: Rahman

first: Nur

last: Ramadanti

first: Hiqmah

middle: Y

last: Yana


title: Composition and RNA binding specificity of metazoan RNase MRP

city: Riverside

first: Shiyang

last: He

address: 3401 Watkins Drive, Boyce Hall

department: Biochemistry

institute: UCR

summary: Ribonuclease (RNase) MRP is a conserved RNA-based enzyme that is essential for maturation of ribosomal RNA (rRNA) in eukaryotes. However, the composition and RNA substrate specificity of this multisubunit ribonucleoprotein complex in higher eukaryotes remain a mystery. Here, we identify NEPRO and C18ORF21 as constitutive subunits of metazoan RNase MRP. Both proteins are specific to RNase MRP and are the only ones distinguishing this enzyme from the closely related RNase P, which selectively cleaves transfer RNA-like substrates. We find that NEPRO and C18ORF21 each form a complex with all other subunits of RNase MRP, stabilize its catalytic RNA, and are required for rRNA maturation and cell proliferation. We harness our discovery to identify a full suite of in vivo RNA targets of each enzyme, including positions of potential cleavage sites at nucleotide resolution. These findings resolve the general composition of metazoan RNase MRP, illuminate its RNA binding specificity, and provide valuable assets for functional exploration of this essential eukaryotic enzyme.

overall_design: E14 mESCs stably expressing Flag-tagged Nepro, Rpp14, Pop5, or Rpp21 were grown and iCLIP experiments were performed for each subunit repeated in four replicates.

first: Yuan

last: Liu

first: Kawon

last: Pyo

first: Shanshan

last: Zheng

first: Meijuan

last: Chen

first: Sihem

last: Cheloufi

first: Nikolai

last: Slavov

first: William

middle: F

last: Marzluff

first: Jernej

last: Murn


title: Effects of extra-tumoral TR11B on gene expression in A549 lung adenocarcinoma cells

city: Shanghai

first: Shiyu

last: Qiu

state: Shanghai

address: West Huaihai Road

institute: Shanghai Jiao Tong University School of Medicine

summary: To investigate the downstream effects of extra-tumoral TR11B, especially the direct role of extra-tumoral TR11B in regulating cell cycle during tumorigenesis, human recombinant TR11B (rhTR11B) was added into the culture medium of A549 cells before RNA-seq was performed.

overall_design: Comparative gene expression profilling analysis of RNA-seq data for A549 cells treated with or without rhTR11B (PBS as negative control).

first: Lifang

last: Ma

first: Keke

last: Yu

first: Qianjun

last: Zhou

first: Yongchun

first: Daolin

last: Tang

first: Jiayi

last: Wang


title: Effects of knockouting OGT or TR11B on gene expression in A549 lung adenocarcinoma cells

summary: To investigate the downstream shared effects of OGT and TR11B, we established A549 OGT-KO and TR11B-KO cells respectively, and performed RNA-sequencing.

overall_design: Comparative gene expression profilling analysis of RNA-seq data for A549 cells and its KO derivatives (OGT-KO or TR11B-KO).


title: A widespread cell atlas of pig skin from embryonic development to postnatal aging

city: Chengdu City

first: Ting

address: No.211, Huimin Road, Wenjiang District

institute: Sichuan Agricultural University

summary: Skin is the largest barrier organ with complex structure and function. We investigated the transcriptional dynamics of pig skin during development and aging at single-cell resolution. Using single-cell RNA sequencing, we profiled the transcriptomes of 443,529 skin cells derived from 30 individuals of 10 developmental time points staged between 56 days of gestation and 7 years old. Our analysis identified the dynamic changes in the cellular transcriptional profile of eight skin cell types at different developmental stages, exhibiting time-dependent skin cell heterogeneity.

overall_design: Skin cells of Chenghua pigs from 10 developmental time points staged, including 56, 66, 76, 86, 105 days of gestation, 3 days old, 90 days old, 180 days old, 3 years od and 7 years old, was obtained by skin tissue disintegration and analysed using scRNA-seq.

first: Rong

last: Yuan

first: Yu

last: Zhang


title: A Microcavity-Based Sarcoma Spheroid Model for Drug Efficacy and Mechanism Analysis Using Cost-effective 3D Printing Technology

status: Public on Aug 04 2025

city: CLEVELAND

first: Yuan

last: Gao

address: 2109 Adelbert Rd., Wood Building Research Tower 300-7, Wood Building Research Tower 300-7

department: Pharmacology

institute: Case Western Reserve University

summary: Ewing sarcoma is a pediatric bone cancer with poor survival in relapsed cases, highlighting the need for better preclinical models. Here, we developed a scalable 3D spheroid platform using SLA-printed microcavity arrays to generate uniform Ewing sarcoma spheroids. High-throughput screening of 11 compounds identified Torin 2, Talazoparib, and Trabectedin as potent inhibitors. Incorporating lung fibroblasts into hybrid spheroids revealed fibroblast-induced drug resistance, mimicking the metastatic tumor microenvironment. Transcriptomic analysis identified activation of NF-κB and TGF-β signaling pathways as key mediators of this resistance. This platform offers a cost-effective, biologically relevant system for drug testing and mechanistic studies in Ewing sarcoma and other stromal-influenced cancers.

overall_design: Hybrid or monoculture spheroids were digested into single cells using trypsin. GFP positive Ewing sarcoma cells were sorted using BD Symphony S6 (CWRU Cytometry & Imaging Microscopy Core), and subject to total RNA extraction using TRIzol according to the manufacturer’s instructions. 250ng of total RNA was used to construct RNA-seq library using the NEBNext UltraExpress RNA Library Prep Kit following manufacturer’s instructions. Briefly, RNA was polyA enriched using NEBNext Poly(A) mRNA Magnetic Isolation Module  and enzymatically fragmented. cDNA was synthesized followed by end repair and adapter ligation, and PCR enrichment with indexed primers. Library was pair end sequenced for 76bp using Illumina NovaSeq platform. Sequencing reads were mapped to reference genome hg38 using RNA STAR with default parameters. Read count tables were created using FeatureCounts with a custom GTF file containing protein coding genes only. Differentially expressed genes were analyzed using DESeq2 with two independent replicates using default parameters. TPM values was calculated using Kallisto.

first: Chao

first: Jaehun

last: Lee

first: Muyi

last: Ye


title: CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity

city: Madrid

first: María

last: Mittelbrunn

state: Madrid

address: C/ Nicolás Cabrera, 1

institute: Centro de Biología Molecular Severo Ochoa

summary: Healthy aging relies on a symbiotic host–microbiota relationship. The age-associated decline of the immune system can pose a threat in this delicate equilibrium. In this work, we investigated how the functional deterioration of T cells can impact host–microbiota symbiosis and gut barrier integrity and the implications of this deterioration for inflammaging, senescence, and health decline. Using the Tfamfl/flCd4Cre mouse model, we found that T cell failure compromised gut immunity leading to a decrease in T follicular and regulatory T (Treg) cells and an accumulation of highly proinflammatory and cytotoxic T cells. These alterations were associated with intestinal barrier disruption and gut dysbiosis. Microbiota depletion or adoptive transfer of total CD4 T cells or a Treg cell–enriched pool prevented gut barrier dysfunction and mitigated premature inflammaging and senescence, ultimately enhancing healthspan in this mouse model. Thus, a competent CD4 T cell compartment is critical to ensure healthier aging by promoting host–microbiota mutualism and gut barrier integrity.

overall_design: To investigate the role of T cells in gut homeostasis in aging-related conditions, we analysed colon transcriptomics in mouse model carrying a specific deletion of Tfam in T cells

first: Manuel

last: Gómez de las Heras

first: Elisa

last: Carrasco

first: Álvaro

last: Fernández-Almeida


title: The deacetylases HDAC1/HDAC2 control JAK2V617F-STAT signaling through the ubiquitin ligase SIAH2

city: Mainz

first: Giuseppe

last: Petrosino

state: --- Select a state ---

address: Ackermannweg 4

institute: Institute of Molecular Biology

summary: Epigenetic modulators of the histone deacetylase (HDAC) family control key biological processes and are frequently dysregulated in cancer. There is superior activity of HDAC inhibitors (HDACi) in patients with myeloproliferative neoplasms (MPNs) that carry the Janus kinase-2 point mutant JAK2V617F. This constitutively active tyrosine kinase activates signal-transducer-and-activator-of-transcription (STAT) transcription factors to promote cell proliferation and inflammatory processes. We reveal that the inhibition of HDAC1/HDAC2 with the clinically advanced HDACi romidepsin, the experimental HDACi entinostat and MERCK60, and genetic depletion of HDAC1/HDAC2 induce apoptosis and long-term growth arrest of primary and permanent MPN cells in vitro and in vivo. This treatment spares normal hematopoietic stem cells and does not compromise blood cell differentiation. At the molecular level, HDAC1 and HDAC2 control the protein stability of SIAH2 through acetylation. Genetic knockout experiments show that SIAH2 accelerates the proteasomal degradation of JAK2V617F in conjunction with the E2 ubiquitin-conjugating enzyme UBCH8. SIAH2 binds to the surface-exposed SIAH degron motif VLP1002 in the catalytic domain of JAK2V617F. At the functional level, SIAH2 knockout MPN cells are significantly less sensitive to HDACi. Global RNA sequencing verifies that JAK-STAT signaling is a prime target of SIAH2. Moreover, HDAC1 is an adverse prognostic factor in patients with acute myeloid leukemia (n = 150, p = 0.02), being a possible complication of MPNs. These insights reveal a previously unappreciated link between HDAC1/HDAC2 as key molecular targets, the still undefined regulation of cytoplasmic-to-nuclear signaling by HDACs, and how HDACi kill JAK2V617F-positive cells from MPN patients and mice with JAK2V617F in vitro and in vivo.

overall_design: We performed gene expression profiling to investigate the impact of inhibition of HDAC1 and HDAC2 by MERCK60 as well as SIAH2 knockout in HEL cells.

first: Al-Hassan

last: Mustafa

first: Marten

last: Fischer

first: Tina

last: Schnöder

first: Désirée

last: Gül

first: Yanira

last: Zeyn

first: Christoph

last: Hieber

first: Johanna

last: Lossa

first: Sabine

last: Muth

first: Markus

last: Radsak

first: Walburgis

last: Brenner

last: Christmann

first: Matthias

last: Bros

first: Florian

last: Heidel

first: Oliver

last: Krämer


title: A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes

status: Public on Aug 03 2025

city: Pittsburgh

first: Sarah

last: Hainer

state: PA

address: 4249 Fifth Ave

department: Department of Biological Sciecnes

institute: University of Pittsburgh

sample_organism:
Saccharomyces cerevisiae
Mus musculus

platform_organism:
Saccharomyces cerevisiae
Mus musculus


title: CFP1 promotes germinal center affinity maturation and restrains and memory B cell differentiation through H3K4me3 modulation

status: Public on Aug 02 2025

city: guang zhou

first: yanan

last: Zhao

state: guang dong

address: No. 74 Zhongshan 2nd Road

institute: SunYat-sen University

summary: Affinity maturation and differentiation of B cells in the germinal center (GC) are tightly controlled by epigenetically regulated transcription programs but the underlying mechanisms are only partially understood. Here we show that CFP1, an integral component of the histone methyltransferase complex Set1A/B, is critically required for GC responses. CFP1 deficiency in activated B cells greatly impairs GC formation with diminished proliferation, somatic hypermutation and affinity maturation. Mechanistically, CFP1 deletion reduces H3K4me3 marks at a subset of cell cycle and GC-related genes and impairs their transcription. Importantly, CFP1 promotes the expression of transcription factors MEF2B and OCA-B and the Bcl6 enhancer-promoter looping for its efficient induction. Accordingly, CFP1-deficient GCB cells upregulate IRF4 and preferentially differentiate into plasmablasts. Furthermore, CFP1 ablation upregulates a panel of pre-memory genes with elevated H3K4me3 and leads to markedly expanded memory B populations. In summary, our study reveals that CFP1-safeguarded epigenetic regulation ensures proper dynamics of GCB cells for affinity maturation and prevents the pre-mature exit from GC as memory cells.

overall_design: We identified the binding patterns of H3K4me3 in normal germinal center B cells and CFP1 knockout germinal center B cells using CUT&Tag. Additionally  we performed RNA-seq in GCB cells to characterize the molecular features after lacking CFP1

first: Yanan

first: Shuoxu

last: Gong

first: Yalin

last: Yang

first: Yimiao

last: Lu

first: Jingning

last: Bai

first: Meiling

last: Liu

first: Wanyu

first: Junchao

last: Dong


title: A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes [MNase-seq]

summary: The nucleosome remodeler Chd1 is required for the re-establishment of nucleosome positioning in the wake of transcription elongation by RNA Polymerase II. Previously, we found that Chd1 occupancy on gene bodies depends on the Rtf1 subunit of the Paf1 complex in yeast. Here, we identify an N-terminal region of Rtf1 and the CHCT domain of Chd1 as sufficient for their interaction and demonstrate that this interaction is direct. Mutations that disrupt the Rtf1-Chd1 interaction result in an accumulation of Chd1 at the 5’ ends of Chd1-occupied genes, increased cryptic transcription, altered nucleosome positioning, and concordant shifts in histone modification profiles. We show that a homologous region within mouse RTF1 interacts with the CHCT domains of mouse CHD1 and CHD2. This work supports a conserved mechanism for coupling Chd1 family proteins to the transcription elongation complex and identifies a cellular function for a domain within Chd1 about which little is known.

overall_design: Micrococcal nuclease DNA-sequencing (MNase-seq) experiment in S. cerevisiae for chromatin fragments including mononucleosomes, subnucleosomes, hexasome-nucleosomes, and dinucleosomes.

last: Tripplehorn

first: Karen

last: Arndt

first: Margaret

last: Shirra

first: Santana

last: Lardo

first: Hannah

last: Marvil


title: A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes [ChIP-seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiment in S. cerevisiae for immunoprecipitated factors HSV-Chd1, HA-Rtf1, Rpb1, H3, H3K4me3, and H3K36me3.


title: Feminization of the Blood Brain Barrier changes the brain transcriptome of Drosophila melanogaster males

status: Public on Aug 01 2025

city: Houston

first: Brigitte

last: Dauwalder

state: TX

address: 3455 Cullen Blvd Rm 342

department: Biology and Biochemistry

institute: University of Houston

summary: Beyond its crucial role as a tight barrier to protect the nervous system, the Blood Brain Barrier (BBB) is increasingly being recognized for its physiological processes that affect brain function and behavior. In Drosophila melanogaster, the BBB expresses sex-specific transcripts, and a change in the sexual identity of adult BBB cells results in a significant reduction of male courtship behavior.  The molecular nature of this BBB/brain interaction is unknown. Here we feminize BBB cells by targeted expression of the Drosophila female specific master regulator TraF in otherwise normal males. We examined the effect on RNA expression in dissected brains by RNA sequencing. We find that 284 transcripts change in comparison to normal males. Transcripts representing cell signaling processes and synaptic communication are enriched, as are hormonal mediators. These transcripts are candidates for the sex-specific interaction between the BBB and the brain circuits that regulate behavior.

overall_design: The blood brain barrier (BBB) of otherwise normal Drosophila males was feminzed by expression of the TraF protein using the Gal4/UAS system. Adult brains were isolated from experimental and control males and RNA extracted. Following Poly-A selection, RNA-seq was performed using paired-end sequencing.

first: Danyel

last: Davis

first: Warda

last: Hashem

first: Josef

last: Reeve

first: Chamala

last: Lama


title: 3D collagen high-throughput screen identifies drugs that induce epithelial polarity and enhance chemotherapy response in colorectal cancer

city: NASHVILLE

first: Marisol

last: Ramirez

state: TENNESSEE

address: 2220 Pierce Avenue, 571 Preston Research Building

department: Center for Quantitative Sciences, Department of Biostatisticss

institute: Vanderbilt University Medical Center

summary: Loss of polarity is a hallmark of cancer, and the related epithelial-to-mesenchymal transition (EMT) phenotype also impacts prognosis and therapy outcomes, particularly in colorectal cancer (CRC). However, the mechanisms and drugs that impact these morphological changes are understudied, due to the complete failure of typical live/dead 2D high-throughput screens to capture morphology or the lack of robustness of 3D screens. We designed a high-throughput screen using 3D type I collagen cultures of CRC cells to assess morphological changes in colonies and identified several FDA-approved drugs that re-epithelialize CRC colonies One of these drugs, azithromycin, increased colony circularity, enhanced E-cadherin membrane localization and ZO-1 localization to tight junctions, caused transcriptomic changes consistent with downregulation of epithelial-to-mesenchymal transition, and elevated sensitivity to the chemotherapeutic, irinotecan. A retrospective analysis of patient data demonstrated that the use of azithromycin in patients undergoing treatment for CRC with irinotecan had improved the 5-year survival compared to the chemotherapy alone. These results highlight the importance of morphological screens to identify novel drug candidates and synergistic mechanisms.

overall_design: SC cells, a CRC cell lines known to form spiky colonies, were seeded in type I collagen cultures and incubated with no drug (control), azithromycin, clindamycin, or linezolid for 12 days. RNA was extracted from colonies and RNA seq profiling completed.

first: Sarah

last: Harmych

first: Qi

first: Bhumindrr

last: Singh


title: A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes [CUT&RUN]

last: Hainer

overall_design: CUT&RUN for H3K4me3, CHD1, H3K36me3, or noab in murine embryonic stem cells


title: ACTN3 genotype influences androgen response in skeletal muscle

city: Parkville

first: Michael

last: See

state: VIC

address: Royal Children's Hospital, 50 Flemington Rd

country: Australia

institute: MCRI

summary: Androgens act through androgen receptor (AR) to maintain muscle mass. Evidence suggests that this pathway is influenced by ACTN3 (α-actinin-3) - “the Gene for Speed”. Given that one in 5 people worldwide lack α-actinin-3, it is possible they may respond to androgens differently. In this study, we show that α-actinin-3 deficiency decreases AR in skeletal muscles of mice and humans (in males and females), and that AR levels positively correlate with α-actinin-3 expression in a dosage dependent manner. α-Actinin-3 deficiency exacerbates gastrocnemius muscle mass loss with androgen deprivation in male mice, and stunts the muscle growth response to dihydrotestosterone at the onset of puberty in female mice. This is mediated by differential activation of pathways regulating amino acid metabolism, intracellular transport, autophagy, mitochondrial activity, MAPK and calcineurin signalling, which may be driven by 7 key genes that are both androgen sensitive and α-actinin-3-dependent in expression. Our results highlight a role for α-actinin-3 in the regulation of muscle mass and suggest that ACTN3 is a genetic modifier of androgen action in skeletal muscle.

overall_design: Effect of Actn3 genotype on response to orchidectomy and DHT treatment. Sample size = 5-6/group. ORCHIDECTOMY: Variables are genotype (WT/KO) and treatment (SHAM/ORX). DHT treatment: Variables are genotype (WT/KO) and treatment (Empty/DHT).

first: Kelly

middle: N

last: Roeszler

first: Lyra

last: Meehan

first: Giscard

last: Lima

first: Alexander

last: Kolliari-Turner

first: Sarah E

last: Alexander

first: Shanie

last: Landen

first: Harrison

last: Wood

first: Chrystal

last: Tiong

first: Weiyi

last: Chen

first: Tomris

last: Mustafa

first: Peter

last: Houweling

first: Nir

last: Eynon

first: Severine

last: Lamon

first: Yannis

last: Pitsiladis

first: David

last: Handelsman

first: Fernando

last: Rossello

first: Mirana

last: Ramialison

first: Kathryn

last: North

first: Jane

last: Seto


title: Single cell approaches define the murine leptomeninges:cortical brain interface as a distinct cellular neighborhood comprised of neural and nonneural cell types

city: Vancouver

first: Freda

last: Miller

state: BC

address: 2185 East Mall

country: Canada

institute: University of British Columbia

summary: The interface between the brain surface and the adjacent meninges is a selective barrier regulating fluid, protein and immune cell exchange between the CNS and periphery. However, the cell types that form this important interface are not yet fully defined. To address this limitation, we have used single cell RNA-sequencing (scRNA-seq) and single cell spatial transcriptomics together with morphological lineage tracing and immunostaining to analyze the adult murine cortex. We show that the cortical interface is comprised of three major cell types, leptomeningeal cells, border astrocytes and tissue-resident macrophages. On the peripheral side the interface is comprised of transcriptionally-distinct PDGFRα-positive leptomeningeal mesenchymal cells that are intermingled with macrophages. This leptomeningeal pial layer is lined by a population of transcriptionally-distinct border astrocytes. The interface neighborhood is rich in growth factor mRNAs, including many leptomeningeal ligands predicted to act on both the border astrocytes and macrophages. On the CNS side of the interface is the relatively cellsparse cortical layer one containing interneurons, microglia, parenchymal astrocytes, oligodendrocyte precursor cells and oligodendrocytes. Except for the border astrocytes, layer one cells are not closely-associated with the interface, suggesting that secreted ligands may be the major way the brain interface communicates with the underlying cortical parenchyma. Thus, our data provide a molecular/cellular resource describing the brain interface cell types and their interactions, thereby enabling future studies asking how this distinct cellular compartment regulates CNS:periphery interactions.

overall_design: High-throughput single cell transcriptomic profiles of the adult mouse brain layer 1 and surrouding immune and meningeal cells from Bl/6 wildtype animals

first: Sarah

last: Ebert

first: Christine

last: Eisner

first: Konstantina

last: Karamboulas

first: Louis-Philippe

last: Bernier

last: Kaplan

first: Brian

last: A MacVicar


title: Endurance training promotes chromatin closure and timely repression of the post-exercise immediate early stress response [ATAC-seq]

city: Basel

first: Laura

middle: Maria

last: de Smalen

state: Basel-Stadt

address: Spitalstrasse 41

department: Biozentrum

institute: University of Basel

summary: Objective: Endurance training is known to elicit numerous changes in skeletal muscle to enhance performance and function. Many of these adaptations are controlled by the modulation of transcriptional programs in myonuclei. While previous studies have explored alterations in DNA methylation and histone modifications in response to exercise, the specific changes in chromatin restructuring and accessibility, a prerequisite for transcription, are still poorly understood. Methods: A multi-omics analysis was performed: ATAC-sequencing was used to map chromatin accessibility in myonuclei isolated from endurance-trained and untrained mice at multiple time points (0h, 6h, and 72h) post-exercise. Gene expression was assessed via RNA-sequencing, and motif activity analysis identified regulatory factors involved in exercise-induced chromatin remodeling and transcriptomic response. Results: Endurance training amplified rapid chromatin closing immediately after exercise, with trained muscle exhibiting a more pronounced loss of chromatin accessibility at 0h and 6h post-exercise compared to untrained muscle. These chromatin accessibility changes persisted longer in trained muscle, with significant retention until 72h post-exercise. Immediate early transcription factors, such as Fos and Jun, showed a training state-dependent shift in activation dynamics. Similarly, specific modulation of genes involved in metabolism, insulin response and angiogenesis was observed. Conclusions: Endurance training triggers rapid and persistent chromatin remodeling in muscle, contributing to the transcriptional response to exercise. Our findings suggest that training induces long-lasting epigenetic changes, potentially underpinning muscle memory and improved physiological resilience. These new insights into the molecular mechanisms of muscle adaptation help to understand the training response, and might become relevant in disease prevention.

overall_design: All conditions (untrained and trained mice sacrificed at 0h, 6h, 72h post-exercise) are compared to sedentary mice that underwent no training nor exercise.

first: Volkan

last: Adak

first: Aurel

middle: B

last: Leuchtmann

first: Konstantin

last: Schneider-Heieck

first: Stefan

last: Steurer

first: Christoph

last: Handschin


title: Single cell approaches define the murine leptomeninges:cortical brain interface as a  distinct cellular neighborhood comprised of neural and nonneural cell types

summary: The interface between the brain surface and the adjacent meninges is a selective barrier  regulating fluid, protein and immune cell exchange between the CNS and periphery. However,  the cell types that form this important interface are not yet fully defined. To address this  limitation, we have used single cell RNA-sequencing (scRNA-seq) and single cell spatial  transcriptomics together with morphological lineage tracing and immunostaining to analyze the  adult murine cortex. We show that the cortical interface is comprised of three major cell types,  leptomeningeal cells, border astrocytes and tissue-resident macrophages. On the peripheral side  the interface is comprised of transcriptionally-distinct PDGFRα-positive leptomeningeal  mesenchymal cells that are intermingled with macrophages. This leptomeningeal pial layer is  lined by a population of transcriptionally-distinct border astrocytes. The interface neighborhood  is rich in growth factor mRNAs, including many leptomeningeal ligands predicted to act on both  the border astrocytes and macrophages. On the CNS side of the interface is the relatively cellsparse  cortical layer one containing interneurons, microglia, parenchymal astrocytes,  oligodendrocyte precursor cells and oligodendrocytes. Except for the border astrocytes, layer one  cells are not closely-associated with the interface, suggesting that secreted ligands may be the  major way the brain interface communicates with the underlying cortical parenchyma. Thus, our  data provide a molecular/cellular resource describing the brain interface cell types and their  interactions, thereby enabling future studies asking how this distinct cellular compartment  regulates CNS:periphery interactions.

overall_design: Multiplexed in situ hybridization-based spatial transcriptomics using the 10X genomics Xenium platform was used to analyze coronal sections adult mouse (C57BL6).

first: David


title: SRCAP mutation promotes cutatneous squamous cell carcinoma invasion [RNA-Seq]

city: Evanston

first: Stephenie

last: Droll

state: IL

address: Hogan 2-100 2205 Tech Drive

department: Molecular Biosciences

institute: Northwestern University

summary: In this study, we identify a mutational hotspot affecting SRCAP in cancer and that SRCAP is recurrently mutated in keratinocyte carcinomas. When introduced to primary human epidermal keratinocytes, the SRCAP hotspot mutation dysregulates gene expression in the differentiated state far more than the progenitor state. Gene dysregulation occurs without a change in H2A.Z chromatin occupancy. Finall, the presence of the SRCAP mutation in a RAS-CDK4 driven model of cSCC increases invasion significantly.

overall_design: This is RNA-seq data of primary human keratinocytes expressing the identified SRCAP mutation in progenitor and differentiated states.

first: Xiaomin

last: Bao


title: Growth signaling promotes H2A.Z deposition by SRCAP to sustain somatic tissue regeneration [RNA-Seq]

summary: In this study, we find that H2A.Z expression and chromatin occupancy dramatically decrease during normal epidermal differentiation. While the chromatin remodeler SRCAP is necessary and sufficient to maintain H2A.Z deposition in epidermal progenitors, EP400 is dispensable. Growth factor signaling mediated by the MAPK and PI3K signaling pathways is necessary to maintain both the expression and deposition of H2A.Z. Loss of SRCAP, H2AZ1, or H2AZ2 induces nuclear deformation and cytoplasmic DNA in progenitor keratinocytes which impairs DNA repair and proliferation.

overall_design:
RNA-sequencing data from H2AZ1, H2AZ2, H2AZ1 + H2AZ2, or SRCAP knockdowns (by shRNA) in progenitor primary human epidermal keratinocytes.
RNA-sequencing data for H2AZ1, H2AZ2, or SRCAP knockdown in the differentiated state.


title: Principles of cotranslational mitochondrial protein import revealed by selective ribosome profiling

city: Pasadena

first: Zikun

last: Zhu

state: CA

address: 1200 E California Blvd

institute: California Institute of Technology

summary: The biogenesis of nearly all mitochondrial proteins begins with translation on cytosolic ribosomes. How these proteins are subsequently delivered to mitochondria remains poorly understood. Here, we systematically investigated the coupling of mitochondrial protein translation and import using selective ribosome profiling in human cells. Cotranslational targeting requires an N-terminal presequence on the nascent protein and contributes to mRNA localization at the mitochondrial surface. This pathway is predominantly used by large, multidomain and topologically complex proteins, whose import efficiency is enhanced when targeted cotranslationally. In contrast to protein targeting to the endoplasmic reticulum (ER), cotranslational mitochondrial import does not favor membrane proteins and initiates late during translation, specifically upon the exposure of a complex globular fold in the nascent protein. Our findings reveal a multi-layered protein sorting system that recognizes both the targeting signal and protein folding status during translation.

overall_design: Selective ribosome profiling of TOM22 in HEK293 cells to investigate cotranslational mitochondrial protein import.

first: Shu-ou

last: Shan


title: Exploring the maize transcriptional regulatory landscape through large-scale profiling of transcription factor binding sites

status: Public on Aug 06 2025

city: Beijing

first: Qiang

last: Huo

address: Yuanmingyuan West Road

institute: China Agricultural University

summary: Understanding gene regulatory networks (GRNs) is essential for improving maize yield and quality through molecular breeding approaches. The lack of comprehensive transcription factor (TF)-DNA interaction data has hindered accurate GRN predictions, limiting our insight into the regulatory mechanisms. In this study, we performed large-scale profiling of maize TF binding sites. We obtained and collected reliable binding profiles for 513 TFs, identified 394,136 binding sites, and constructed an accuracy-enhanced maize GRN (mGRN+) by integrating chromatin accessibility and gene expression data. The mGRN+ comprises 397,699 regulatory relationships. We further divided the mGRN+ into multiple modules across six major tissues. Using machine-learning algorithms, we optimized the mGRN+ to improve the prediction accuracy of gene functions and key regulators. Through independent genetic validation experiments, we further confirmed the reliability of these predictions. This work provides the largest collection of experimental TF binding sites in maize and highly optimized regulatory networks, which serve as valuable resources for studying maize gene function and crop improvement.

overall_design: The transcriptional landscape of maize


title: De Novo Design of Integrin α5β1 Modulating Proteins for Regenerative Medicine

city: Seattle

first: Xinru

last: Wang

state: Washington

address: 3946 W Stevens Way NE

institute: University of Washington

summary: Integrin α5β1 is crucial for cell attachment and migration in development and tissue regeneration, and α5β1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5β1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5β1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine.

overall_design: MCF 10A, MSC, hOBS, and hFF cells were treated with integrin a5 B1 agonists or antagonists on plastic or titatnium surfaces to compare the effects of the de novo binders on cell transcriptomes

first: Jordi

last: Guillem

first: Saurav

last: Kumar

last: Lee


title: Starvation induced circulating miR-33a secretion remodeled extracellular matrix of tumor microenvironment by altering polyamine metabolism  [miRNA-Seq]

city: Wuhan

first: Yan

last: Wei

address: Bayi road 229

institute: wuhan university

summary: Breast cancer cells secret different kinds of cargoes through extracellular vesicles (EVs) especially under stress conditions. However, the underling mechanism and function is poorly defined. Here, we found RNA binding protein ACO1 could bind miR-33a and assist their package into EVs in tumor core region. Thereby, miR-33a suppressed putrescine metabolism in cancer-associated fibroblasts (CAFs)  and reprogrammed H3K4me3 mediated epigenetic regulation. Chip-seq data suggested stress granules related genes were downregulated and ECM related genes were upregulated. Most notably, putrescine inhibited KDM5C expression level but did not altered activity. Finally, our study provides a novel mechanism of how cancer EVs reprogrammed polyamine metabolism in tumor stroma, leading to spatially different distribution of ECM in tumor microenvironment.

overall_design: Comparative miRNA expression profiling analysis of small RNA deep data sequencing for EVs

first: Sheng

last: Hu

first: Wei

last: Yan


title: Starvation induced circulating miR-33a secretion remodeled extracellular matrix of tumor microenvironment by altering polyamine metabolism [CAF EV]

overall_design: Comparative gene expression profiling analysis of RNA-seq data for EV treated CAFs


title: Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma

status: Public on Jul 31 2025

city: Heidelberg

first: Cihan

last: Erkut

address: Im Neuenheimer Feld 581

department: Applied Functional Genomics

institute: German Cancer Research Center

summary: The embryonic transcription factor TBXT (brachyury) drives chordoma, a spinal neoplasm without effective drug therapies. TBXT’s regulatory network is poorly understood, and strategies to disrupt its activity for therapeutic purposes are lacking. We developed designed ankyrin repeat proteins that block TBXT-DNA binding (T-DARPins). In chordoma cells, T-DARPins reduced cell cycle progression, spheroid formation, and tumor growth in mice and induced signs of senescence and differentiation. Transcriptomic and proteomic analyses identified gene networks involved in cell cycle regulation, embryonic cell identity, and interferon response and revealed features of regulome components, such as susceptibility to pharmacologic inhibition and the fine-tuning of TBXT downstream effectors through IGFBP3. Finally, we found high interferon signaling in chordoma cell lines and patient tumors, which was promoted by TBXT and associated with sensitivity to JAK2 inhibitors. These findings demonstrate the potential of DARPins for probing nuclear proteins to understand the regulatory networks of transcription factor-driven cancers, including entry points for therapies that warrant testing in patients.

overall_design:
We aimed to investigate the effect of DARPin-mediated TBXT inhibition on the transcriptomes of UM-Chor1 chordoma cells.
DARPins were expressed via transducing cells with pLenti6.2-V5/DEST encoding control DARPin E3_5 or T-DARPins A2, B1, and D4. Each experiment was performed in triplicates.

first: Charles

last: Umbaugh

first: Andreas

last: Plückthun

last: Fröhling

first: Claudia

last: Scholl


title: Systemic inflammation-induced adipose tissue remodeling drives psoriasis exacerbation in obesity through epigenetic and immunometabolic dysregulation

city: Inchon

first: YunJae

last: Jung

address: 155 Gaetbeol-ro, Yeonsu-gu

department: Microbiology

country: South Korea

institute: College of Medicine, Gachon University

summary: Obesity has been known to be associated with psoriasis, negatively affecting its prevalence, severity, and treatment response. However, a detailed systemic inflammatory microenvironment in obesity-associated psoriasis has not been extensively investigated. To explore this further, we used a mouse model of psoriasis induced by topical application of imiquimod or injection of IL-23. We found that obese mice exhibited systemic inflammatory responses when exposed to imiquimod, with increased expression of inflammatory cytokines in the skin and elevated serum levels of mediators implicated in psoriasis pathogenesis. Notably, imiquimod also caused a significant decrease in body weight and fat, which was more pronounced in obese mice, resulting a thinner subcutaneous fat layer. Further analysis revealed higher macrophage infiltration, upregulated genes relating to the inflammatory response, and increased expression of necrosis-associated molecules in the perigonadal fat of imiquimod-treated obese mice than in lean mice. IL-23 injection induced comparable pathogenic features of psoriatic inflammation in obese and lean mice without causing adipose tissue destruction or systemic increase of inflammatory mediators.

overall_design: At 8 weeks of age, mice were divided into two groups and were fed either a high-fat diet (HFD) or a standard chow diet for a duration of 12 weeks. Throughout the study, both groups of mice underwent daily topical applications of 62.5 mg of IMQ cream (5%) (Aldara™) on their shaved backs for five consecutive days. Additionally, to induce intradermal IL-23-induced psoriatic skin inflammation, the mice received daily injections of 1 μg of rmIL-23 in PBS at a specified location on their shaved backs for five days.

first: Hee

last: Kim

first: Jinsun

last: Jang


title: IWS1 Stimulates Pol II Transcription Elongation In Vivo [RNA-Seq]

status: Public on Jul 30 2025

city: Göttingen

first: Kristina

last: Žumer

address: Am Faßberg 11

department: Department of Molecular Biology

institute: Max Planck Institute for Multidisciplinary Sciences

summary: Interacts with SPT6 1 (IWS1) has been implicated in various co-transcriptional processes, yet its direct role in RNA Polymerase (Pol) II transcription in vivo remains elusive. In this study, we utilized a rapid depletion system of IWS1 in human cells, followed by multi-omics analysis and biochemical assays, to elucidate its function. We show that IWS1 depletion results in a global decrease of RNA synthesis, but does not affect the chromatin recruitment of the histone methyltransferase SETD2. In vivo and in vitro analyses of nascent transcription and histone modifications revealed that the observed decrease in methylation is a secondary effect of the transcription defect caused by IWS1 depletion. Whereas these results show that IWS1 is essential for maintaining normal RNA Pol II elongation velocity in vivo, and that it can directly stimulate transcription.

overall_design: Samples for each condition were collected in biological duplicates. Cells were treated with dTAG7 for 1 hour, the corresponding control cells were treated for the same duration with the solvent only (DMSO) at the same vol/vol dilution.

first: Aiturgan

last: Zheenbekova

first: James

last: Walshe

first: Moritz

last: Ochmann

first: Ute

last: Neef

first: Kerstin

last: Maier

first: Petra

last: Rus

first: Yumeng

first: Henning

last: Urlaub

last: Zumer

first: Patrick

last: Cramer


title: A direct interaction between the Chd1 CHCT domain and Rtf1 controls Chd1 distribution and nucleosome positioning on active genes [ATAC-seq]

first: Sarah

last: Hainer

overall_design: ATAC-seq in murine embryonic stem cells

last: Tripplehorn

first: Karen

last: Arndt

first: Margaret

middle: K

last: Shirra

first: Santana

last: Lardo

first: Hannah

last: Marvil


title: A spatial single-cell atlas of the claustro-insular region uncovers key regulators of neuronal identity and excitability

status: Public on Jul 29 2025

city: Geneva

first: Ivan

last: Rodriguez

address: 30 quai Ernest Anrsermet

department: Genetics and Evolution

institute: University of Geneva

summary: The claustro-insular region is an evolutionarily conserved and extensively interconnected brain area, critical for functions such as attention, cognitive flexibility, interoception, and affective processing. Despite its importance, its cellular composition and organization remain poorly characterized, hindering a comprehensive understanding of the mechanisms underlying its diverse functions. By combining single-cell RNA sequencing and spatial transcriptomics, we create a high-resolution atlas of this region in mice, uncovering distinct neuronal subtypes and unexpected complexity. Leveraging this atlas, we investigate the role of NR4A2, a neuropsychiatric risk factor expressed in several claustro-insular neuronal subtypes. In an Nr4a2 haploinsufficiency model, we find that only claustrum neurons exhibited shifts in molecular identity. This identity shift, which involves the activation of a transcription factor cascade, is associated with alterations in neuronal firing activity. Our findings provide new insights into the cellular architecture of the claustro-insular region and highlights Nr4a2 as a key regulator of its component’s identities.

overall_design: Characterizing the genetic diversity of claustro-insular neurons in adult wild-type and Nr4a2 heterozygous mice using single-cell RNA sequencing

first: Leon

last: Fodoulian

first: Madlaina

last: Boillat

first: Marie

last: Moulinier

first: Alan

last: Carleton