Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CITEseq of hepatic CD4+ T cells from healthy mice and mice with steatohepatitis

ABSTRACT: Unresolved inflammation and fibrosis are the two key features of metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of steatotic liver disease that can evolve into cirrhosis and liver cancer. To better understand the role of CD4⁺ T cells in the pathogenesis of MASH, we comprehensively characterized hepatic CD4⁺ T cells in murine MASH at a single-cell protein and transcriptional level. CITE-sequencing revealed a marked shift in intrahepatic CD4⁺ T-cell composition in MASH, with enrichment of Th1, regulatory, and cytotoxic CD4⁺ T cells. Transcriptomic profiling also identified Tnfrsf4 (OX40) upregulation in hepatic CD4⁺ T cells during MASH. Together, these studies provide a proteogenomic single-cell atlas for hepatic CD4⁺ T cells and uncover a CD4⁺ T cell-dependent immunopathogenic circuit as a promising immunotherapeutic target to alleviate MASH and liver fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE301733 | GEO | 2026/05/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Quantitative proteomics analysis of liver from LONP1 Knockout mice

Project description:The mechanisms of hepatic stellate cell (HSC) activation and the development of liver fibrosis remains largely unknow. Here, we revealed a fibrosis related mechanism of hepatocytes-HSCs crosstalk regulated by hepatocyte LONP1. We demonstrate that hepatocyte LONP1 expression is decreased in HFD-fed mice and MASH patients. Liver-specific LONP1 deficiency increases orotic acid level and aggravates MASH-induced liver fibrosis in mice. We have identified DHODH as a substrate that is selectively degraded by LONP1 in an ATP-dependent manner. Moreover, activation of LONP1 reduces orotic acid levels and alleviates MASH-induced fibrosis in mice. Mechanistically, LONP1 mediates DHODH turnover, maintaining lower orotic acid levels to inhibit ATF3-mediated HSC proliferation and activation, thereby preventing liver fibrosis. Furthermore, plasma orotic acid levels are negatively correlated with liver LONP1 levels in humans. Therefore, targeting LONP1-mediated hepatocyte-HSC communication may represent a promising therapeutic strategy for MASH-induced liver fibrosis.

2025-09-23 | PXD055467 | Pride

NTN1 cell-autonomously promotes fibrotic response in HSCs.

Project description:Liver fibrosis is a hallmark of progressive liver diseases including metabolic dysfunction-associated steatohepatitis (MASH). Activated hepatic stellate cells (HSCs) are responsible for the excessive synthesis of extracellular matrix(ECM) proteins and collagen deposition in the liver, leading to progressive loss of hepatic functions. However, the nature of paracrine and autocrine signals driving HSC activation and fibrotic response within the liver microenvironment remains incompletely delineated. Here we uncover Netrin-1 (NTN1) as a crucial HSC-derived autocrine factor that promotes HSC activation and liver fibrosis. Hepatic NTN1 mRNA and protein levels were elevated during fibrosis associated with MASH and CCl4-induced liver injury. Hepatic NTN1 overexpression exacerbated diet-induced MASH pathologies and CCl4-induced liver fibrosis. Conversely, HSC-specific conditional ablation of NTN1 alleviated the progression of liver fibrosis. Mechanistic studies using cultured HSCs demonstrated that NTN1 promoted HSC activation in a cell-autonomous manner via a UNC5B and Ca2+-dependent signaling pathway. These findings illustrate the causative role of NTN1-mediated autocrine signaling in driving HSC activation and fibrotic response during liver disease, suggesting potential therapeutic targets for anti-fibrosis therapy.

2026-02-25 | GSE303583 | GEO

NTN1 cell-autonomously promotes fibrotic response in HSCs

2026-02-25 | GSE285431 | GEO

Therapeutic Targeting of AREL1 in Hepatic Stellate Cells Attenuates MASH-related Liver Fibrosis [scRNA-seq]

Project description:Fibrosis resulting from metabolic-associated steatohepatitis (MASH) is increasingly recognized as the predominant form of liver fibrosis. Although the activation of hepatic stellate cells (HSCs) is essential for liver fibrosis, the mechanisms underlying HSC activation in MASH remain inadequately understood. Integrated analysis of large-scale sc/snRNA sequencing data from human healthy and fibrosis samples revealed a distinct subpopulation of HSCs in MASH. AREL1 is a characteristic gene of this subpopulation and is uniquely upregulated in MASH-related fibrosis. HSC-specific knockout of AREL1 markedly attenuated liver fibrosis in MASH model male mice. Mechanistically, AREL1 is regulated by cholesterol and facilitates HSC activation through the AREL1-ILK axis, subsequently activating the PI3K–AKT signaling pathway. Moreover, therapeutic knockdown of AREL1 using vitamin A-modified lipid nanoparticles markedly ameliorated MASH-related liver fibrosis. Here, we show a unique mechanism underlying HSC activation in MASH-driven fibrosis and presents the targeted knockdown of AREL1 in HSCs represents a novel therapeutic avenue.

2026-05-21 | GSE327949 | GEO

Therapeutic Targeting of AREL1 in Hepatic Stellate Cells Attenuates MASH-related Liver Fibrosis [RNA-Seq]

2026-05-21 | GSE328089 | GEO

Effects of engineered IL-18BP on attenuation of hepatic stellate cell activation

Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease associated with hepatic inflammation and fibrosis. Inflammasome-mediated IL-18 signaling is enhanced under MASH condition. IL-18 binding protein (IL-18BP) is a soluble protein that can block IL-18 actions and therapeutic potential of IL-18BP for MASH-induced fibrosis is largely unknown. We newly developed a human IL-18BP biologics (APB-R3) and injected it to mice to evaluate its pharmacologic efficacy. APB-R3 strikingly abolished hepatic fibrosis and reduced collagen markers. We further investigated whether APB-R3 could inhibit fibrotic activation of hepatic stellate cells (HSCs). This study proposes that abrogation of IL-18 signaling by boosting IL-18BP can strongly inhibit the development of MASH-induced fibrosis and our engineered IL-18BP biologics can become promising therapeutic candidate for curing MASH.

2024-10-18 | GSE279499 | GEO

Effects of engineered IL-18BP on attenuation of MASH liver

2024-10-18 | GSE279496 | GEO

Lower H2S-generating enzyme levels and persulfidation-mediated protein protection characterize metabolic dysfunction-associated steatohepatitis

Project description:Metabolic dysfunction–associated steatohepatitis (MASH), marked by hepatic steatosis and inflammation, is a major risk for cirrhosis and liver cancer. Obesity-induced oxidative stress plays a central role in MASH promoting protein damage and dysfunction. Cysteine persulfidation (PSSH), a post-translational modification regulated by hydrogen sulfide (H2S), is involved in protein stability and cellular protection. However, the role of PSSH in MASH is poorly understood. We found that H2S-producing enzymes are downregulated in livers with fibrosis and inflammation, leading to decreased hepatic PSSH. Using dimedone-switch-based mass spectrometry, we mapped the alterations in the liver persulfidome during diet-induced fibrosis and inflammation. While the levels of H2S-producing enzymes dropped, some proteins, including protein tyrosine phosphatases (PTPs) and redox regulators, showed increased PSSH. This change suggests that H2S-mediated persulfidation helps protect proteins from oxidative damage. Overall, decreased H2S enzyme expression and reduced PSSH may impair protection against oxidative stress, contributing to liver dysfunction in obesity.

2025-08-04 | PXD057932 | Pride

PAD4⁺ Neutrophils Promote Hepatic Stellate Cell Activation and Accelerate MASH Fibrosis Progression via NETs-DNA/TAOK1/MAPK Pathways

Project description:Neutrophils play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH) by mediating inflammatory responses. However, the heterogeneity of neutrophil subsets in MASH and their specific contributions to disease progression remain unclear. In this study, analysis of liver biopsies from 265 patients revealed a strong association between elevated neutrophil counts and MASH severity, particularly fibrosis. Five distinct neutrophil subsets were identified in human liver tissue, with PAD4⁺ neutrophils serving as key drivers in MASH progression. Mechanistically, PAD4⁺ neutrophils generate neutrophil extracellular traps (NETs) and activate hepatic stellate cells via the TAOK1-dependent MAPK signaling pathway. Inhibition of PAD4⁺ neutrophils in vivo attenuated the progression of liver fibrosis without exacerbating liver injury. Collectively, these findings elucidate the pivotal involvement of PAD4⁺ neutrophils in MASH progression and identify them as promising therapeutic targets for mitigating fibrosis and inflammation.

2025-11-07 | GSE308064 | GEO

GDF10 cell-autonomously alleviates fibrotic response in HSCs

Project description:Liver fibrosis has emerged as the primary determinant of outcomes in metabolic dysfunction associated steatohepatitis (MASH). Quiescent hepatic stellate cells (HSCs) differentiate into activated HSCs or myofibroblasts, which drives liver fibrosis and contribute to the progressive loss of hepatic function. However, the underlying mechanisms of autocrine signals driving and reversing HSC activation and fibrotic response within the liver microenvironment remains incompletely delineated. Here, through searching for cytokines highly enriched expression in HSCs compared to other liver cell types by single-cell transcriptomic analysis, we found that Gdf10 is specifically expressed in HSCs, whereas its protein levels were elevated during fibrosis associated with MASH and CCl4-induced liver injury. The functional importance of GDF10 in alleviating the progression of liver fibrosis was demonstrated using gain and loss of GDF10 function mice and cultured HSCs treated with GDF10. Furthermore, the novel HSC-targeted delivery strategy of Gdf10 mRNA in fibrosis mice reversed their fibrotic phenotypes. These results reveal a new regulatory pathway in MASH microenvironment, suggesting a promising strategy for delivering drugs that can shift HSC functions to restore HSC balance.

2025-12-04 | GSE303711 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data