Bulk Liver in MAFLD/MASH
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ABSTRACT:
PROVIDER: PRJNA1109378 | ENA |
REPOSITORIES: ENA
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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: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:Bulk White Blood Cells in MAFLD/MASH
| PRJNA1109377 | ENA
Project description:Single-cell landscape of peripheral immune cells in MAFLD/MASH
| PRJNA1110221 | ENA
Project description:Transcriptomic analysis was applied to liver tissues of seven patients with MAFLD and nine normal controls,then, differential genes were identified by comparative analysis of sequencing results, and target genes that may be related to the pathogenesis of MAFLD were further studied.This study may provide new ideas for understanding the pathogenesis of MAFLD and thus provide new targets for the treatment of MAFLD.
2021-12-14 | GSE183229 | GEO
Project description:Understanding mechanisms causing MAFLD (Metabolic Associated Fatty Liver Disease) and its progression to MASH (metabolic dysfunction-associated steatohepatitis) is clinically important and scientifically challenging. Hepatic insulin resistance is a common component in the progression of MAFLD in patients and experimental animals; however, hepatic steatosis caused by the HFD45% (high-fat diet) decreases during chronic hepatic IR generated by inactivation of Irs1/2 (LDKO), AKT1/2, or InsR 1-3—which is inconsistent with the expected relationship between IR and MAFLD in humans4. Here we found that complete hepatic insulin resistance promotes the fructose-enriched GAN diet-induced MAFLD, including acute inflammation and MASH in LDKO mice. Unexpectedly, fructose phosphorylation catalyzed by hepatic Khk (ketohexokinase) was not required as acute MAFLD progressed strongly in LDKOKhkL/L mice fed the GAN diet. FoxO1 activated during hepatic IR induces Fst (Follistatin) expression and secretion from the liver of LDKO mice. Inactivation of hepatic FoxO1 in LTKO mice (LDKO•FoxO1L/L) or Fst in LDKOFstKO mice prevented acute MAFLD during the GAN diet. Consistently, overexpression of hepatic Fst promoted GAN diet-induced MAFLD/MASH and hepatic carcinoma. Mechanistically, circulating Fst promoted adipose tissue IR and lipolysis, which can deliver FFA (free fatty acid) to the liver for esterification with excess Gro3P (glycerol 3-phosphate) generated by fructose metabolism, although hepatic DNL (de novo lipogenesis) decreased strongly in LDKO mice while. Since circulating FST correlates positively with both T2D and MAFLD in humans, our results suggests that hepatic FST induced by progressive hepatic IR might promote MAFLD/MASH during the consumption of sugar-sweetened food and beverages consumed frequently by people and animals with T2D.
2024-06-23 | GSE270246 | GEO
Project description:Recent studies have highlighted the beneficial effect of resolvin D1 (RvD1), a DHA-derived specialized pro-resolving mediator, on metabolic dysfunction-associated steatohepatitis (MASH), but the underlying mechanisms are not well understood. Our study aims to determine the mechanism by which RvD1 protects against MASH progression. RvD1 was administrated to MASH mice, followed by bulk and single-cell RNA sequencing analysis. Primary cells including bone marrow-derived macrophages (BMDMs), Kupffer cells, T cells, and primary hepatocytes were isolated to study the effect of RvD1 on inflammation, cell death, and fibrosis regression genes. RvD1 administration improved MASH features including reducing inflammation, cell death, and liver fibrosis. Mechanistically, RvD1 reduced inflammation by suppressing the stat1-cxcl10 signaling pathway in macrophages and prevented cell death by alleviating ER stress-mediated apoptosis in hepatocytes. Moreover, RvD1 induced Mmp2 and decreased Acta2 expression in hepatic stellate cells (HSCs), and promoted Mmp9 and Mmp12 expression in macrophages, leading to fibrosis regression in MASH. RvD1 reduced stat1-mediated pro-inflammatory response, mitigated ER stress-induced apoptosis, and promotes MMP-mediated fibrosis regression in MASH. Thus, our study highlights the therapeutic potential of RvD1 for MASH.
2025-04-25 | GSE263768 | GEO
Project description:Non-alcoholic steatohepatitis (NASH) represents a significant and growing public health concern worldwide, characterized by hepatic steatosis, inflammation, and varying degrees of fibrosis. In vitro models of NASH play a crucial role in elucidating the underlying mechanisms of disease pathogenesis, identifying potential therapeutic targets, and evaluating the efficacy of pharmacological interventions. Several preclinical models of MASH have been developed and are being used extensively to study these areas. While standard cell culture models allow for elucidation of certain molecular pathways involved in MASH pathogenesis, they lack three-dimensional architecture and cellular heterogeneity observed in native liver tissue, potentially limiting their physiological relevance and inability to fully capture the multifactorial nature of the disease Precision cut liver slices from MASH livers retain the complex multicellular architecture of the liver including hepatocyte arrangement, sinusoidal structure, and cellular interactions, but the metabolism deteriorates over a short period of time (usually reported as 2 days). Human liver organoids from iPSCs (induced pluripotent stem cells) retain the genetics of the patients but fail to fully differentiate into hepatocytes or have the liver architecture. Human liver spheroids incubated in a MASH cocktail develop several phenotypic characteristics of a MASH liver, but the small spheroid size precludes extensive histological comparisons to MASH livers. Microphysiological systems (MPS) or “liver on a chip” in which 3D cultures are perfused, maintain many of the physiological functions of the liver owing to precise control over microenvironmental parameters, including fluid flow, nutrient gradients, and mechanical cues. However, MPS are difficult to scale up and have not been developed to reproduce a MASH phenotype. In comparison, bioprinted liver tissues for MASH have many advantages. Organovo’s 3D bioprinted liver tissues are comprised of all major primary liver cells including hepatocytes, endothelial cells, stellates and Kupffer cells, mixed in physiologically relevant ratios. These cells are then bioprinted in precise pre-defined liver specific geometries to recapitulate complexity of the hepatic microenvironment.. This mimicking of tissue architecture enables more accurate representation of cellular interactions, spatial organization, and microenvironmental cues crucial for MASH pathogenesis. The liver tissues developed using this method maintain differentiation and metabolism over several weeks. In this paper, we further demonstrated that upon treatment with a MASH induction cocktail, these liver tissues respond accurately by developing steatosis and fibrosis Tissue response varies depending in response to the complexity of the MASH cocktail.
2024-11-29 | GSE280378 | GEO
Project description:Single-cell landscape of peripheral immune cells in MAFLD/MASH [scRNA-seq]
| PRJNA1109376 | ENA