MASH Mouse Model Transcriptomic Characteristics
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE295230 | GEO | 2026/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of cirrhosis and liver related mortality, but it remains unclear how nutrient stresses drive coordinated transcriptional remodeling in the pathogenesis of MASH. Clinical studies reported that methionine and choline deficiency (MCD) promotes chronic liver diseases. Multiple types of MCD diets have been adopted to establish MASH mouse models. However, how methionine and choline deficiency modulates cell-intrinsic transcriptional responses across parenchymal and nonparenchymal liver cell types, and whether these effects recapitulate human MASH, remains unclear. Here, we generated a customized MCD cell culture medium to induce nutrient stress in HepG2 cells, endothelial cells, bone marrow derived macrophages, and hepatic stellate cells (HSCs). RNA sequencing was performed to characterize transcriptional regulations in response to MCD. Across cell types, lack of methionine and choline induced transcriptional program of inflammatory and stress response and suppressed metabolic pathways and cell-cycle progression, suggesting a proliferation pause as a compensatory stress-adaptive response that preserves cell viability and essential functions. In addition to these shared responses, MCD stress also caused distinct cell type-specific outputs that could contribute to the pathogenesis of MASH. Integrated analysis of these datasets with human MASH liver single nucleus transcriptomic data demonstrated that MCD condition recapitulates multiple pathophysiological features of human MASH, including the elevated inflammation, enhanced hepatocyte death, disrupted redox balance, altered metabolic homeostasis, and HSC activation. These findings not only uncover how MCD stress promotes MASH progression, but also provide a conceptual basis to guide future use of MCD diet-induced models in MASH studies.
2026-03-25 | GSE319635 | GEO
Project description:Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to steatohepatitis (MASH) and is a major cause of liver cirrhosis. In the early disease stage, liver inflammation is absent. However, the early involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study. Patients have been histologically stratified and characterized by liver bulk RNA-Seq.
2025-04-30 | GSE267031 | GEO
Project description:Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to steatohepatitis (MASH) and is a major cause of liver cirrhosis. In the early disease stage, liver inflammation is absent. However, the early involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study characterized by White Blood bulk RNA-Seq.
2025-04-30 | GSE267032 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as the leading cause for liver transplantation worldwide. MASH is chatacterized by hepatic lipid accumulation, inlammation and fibrosis which is associaed with worst outcome in patients sufferreing from this pathology. Using the murine choline deficient amino acid defined high fat diet (CDAA-HFD) model of MASH we showed that Ephb2-specific deletion in HSCs using the tamoxifen inducible PdgfCre-eRT2 promoer driver is sufficient to mitigate MASH fibrosis in mice.
2026-01-31 | GSE274899 | GEO
Project description:Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to metabolic dysfunction-associated steatohepatitis (MASH) and is a major cause of liver cirrhosis. Although liver inflammation is the hallmark feature of MASH vs MAFLD, the involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study. Patients have been histologically stratified and further characterized by liver bulk RNA-Seq. Peripheral immune cells from patients and control blood samples have been comprehensively profiled using bulk and single RNA-Seq. Results: 22 patients with fibrosis stage less then F3 have been histologically stratified into patients with low, medium and high disease activity score (NAS). In contrast to fibrosis, NAS group correlated with non-invasive imaging readouts and blood biomarkers of liver damage and inflammation (ALT, AST). Prevalence of type 2 diabetes and obesity was increased with NAS stage. Bulk RNA-seq profiling of patient liver biopsies revealed gene signatures that were positively and negatively associated with NAS. Known marker genes for liver fibrosis where up-regulated on RNA level. Blood bulk RNA-sequencing showed only moderate differences in patients versus healthy controls. In contrast, single cell analysis of white blood cells revealed multiple alterations of immune (sub-) populations including increased abundance of immature B-cells and myeloid suppressor cells in MAFLD/MASH patients as well as disease-association of neutrophil sub-populations.
2025-04-30 | GSE267033 | GEO
Project description:Limonin (Lim), a triterpenoid predominantly enriched in citrus fruits, exhibits diverse pharmacological activities, yet its therapeutic efficacy and mechanistic basis in metabolic dysfunction-associated steatohepatitis (MASH) remain poorly defined. Here, we show that Lim attenuates liver fibrosis and hepatocellular apoptosis in MASH mouse models induced by a methionine–choline-deficient (MCD) diet.
2026-04-30 | GSE328199 | GEO
Project description:This study investigated the effects of Eleutheroside E on hepatic gene expression in metabolic dysfunction-associated steatohepatitis (MASH). A high-fat diet-induced MASH mouse model was established, and liver tissues from control, MASH model, Eleutheroside E-treated MASH, and resmetirom-treated MASH groups were collected for RNA-seq analysis.
2026-06-16 | GSE335225 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by steatosis, inflammation, and fibrosis. However, the mechanisms linking lipid droplet (LD) metabolism to MASH progression remain poorly understood. AF6 is a polarity protein known to regulate metabolic homeostasis, but its role in the development of MASH remains largely undefined. Here, we identify AF6 as a critical regulator of hepatic lipid accumulation and inflammation in MASH. Hepatic AF6 expression is elevated in MASH patients and diet-induced mouse models. Liver-specific deletion of AF6 attenuated steatosis, inflammation, and fibrosis in both high-fat, high-cholesterol (HFHC) and choline-deficient, amino acid-defined high-fat diet (CDA-HFD)-induced MASH models. Mechanistically, lipid overload promotes nuclear translocation of AF6, which interacts with the transcription factor C/EBPβ and enhances its nuclear accumulation. This interaction increases transcription of the lipid droplet fusion protein CIDEA, promoting LD growth and lipid deposition. AF6 also exacerbates MASH by enhancing C/EBPβ-mediated proinflammatory signaling. Restoration of CIDEA expression in AF6-deficient mice reverses the protective effects. In human liver biopsies and iPSC-derived liver organoids, the AF6–C/EBPβ–CIDEA axis is upregulated and correlates with disease severity. Importantly, a CRISPR-Cas9–based lipid nanoparticle (LNP) therapy targeting AF6 effectively reduced lipid accumulation, inflammation, and fibrosis in MASH mice and organoids. AF6 promotes MASH progression by facilitating C/EBPβ nuclear localization and transcriptional activation of CIDEA. Targeting the AF6–C/EBPβ–CIDEA axis represents a promising therapeutic strategy for treating MASH.
2026-02-18 | GSE305662 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis represent distinct yet interconnected pathological processes underlying chronic liver disease progression. While high-fat diet (HFD)-induced MASH models recapitulate metabolic inflammation, carbon tetrachloride (CCl₄)-induced models capture toxicant-driven fibrogenesis. Here, we performed single-cell RNA sequencing (scRNA-seq) on liver tissues from HFD-induced MASH and CCl₄-induced fibrosis mouse models to construct a high-resolution atlas of liver cellular heterogeneity. This work establishes a valuable resource for dissecting liver disease mechanisms, enabling targeted therapeutic discovery and offering a framework for integrating diverse preclinical models of chronic liver injury.
2026-06-18 | GSE300744 | GEO
