Visium Mouse liver
GSM8114830
mouse liver fibrotic liver disease 38 MB 2,577 obs silver H&E
TechnologyVisium
Organismmouse
Tissueliver
Conditionfibrotic liver disease
Obs2,577
silver H&E
Collections / Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release in a spatial manner to amplify liver fibrosis
Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release in a spatial manner to amplify liver fibrosis
Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and the release of fibrogenic nano-sized extracellular vesicles (EVs). Activated HSCs increase their glucose metabolism via glycolysis to satisfy high energy demands. Nevertheless, the mechanism of how glycolysis in HSCs coordinates fibrosis amplification in the fibrogenic zones in the liver is elusive and is the scope of this study. Single cell RNA sequencing (scRNAseq) and bulk RNAseq demonstrated that several glycolysis enzymes, including hexokinase 2 (HK2), were upregulated in activated HSCs. HSC-selective glycolysis-deficient mice (HK2ΔHSC) showed abrogated CCl4-mediated fibrosis as compared to littermate controls (HK2fl/fl). Spatial transcriptomics revealed an upregulation of several EV-related pathways in the fibrotic pericentral zone during liver fibrosis in control HK2fl/fl mice. However, glycolysis-deficient HK2ΔHSC mice showed downregulation of these EV-related pathways in the pericentral zone. Consistently, induction of glycolysis in HSCs in vitro, either by glucose or platelet-derived growth factor B (PDGF), upregulated the expression of several extracellular vesicle (EV)-related genes, including RAB31. Glycolysis in HSCs epigenetically enhanced RAB31 expression through histone-3 lysine-9 acetylation (H3K9ac) on the promoter region, leading to increased EV release. Functionally, glycolysis-dependent EVs were enriched with fibrogenic molecules and increased the expression of fibrotic markers in recipient HSCs. Finally, EVs derived from glycolysis-deficient HK2ΔHSC mice abrogated liver fibrosis amplification as compared to EVs derived from littermate control HK2fl/fl mice. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the pericentral fibrotic regions in the liver.
Datasets2
Size~81 MB
AssayVisium
Samplemouse · liver
KindComparison
Download the whole collection
Python · lamindb
import lamindb as ln
import spatialdata as sd
coll = ln.Collection.get(key="geo-gse259363")
coll.ordered_artifacts.df() # the 2 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]
# …or load each straight into memory as a SpatialData object:
sdatas = {a.key: sd.read_zarr(a.cache()) for a in coll.ordered_artifacts.all()}Member datasets · 2
Visium 
Visium Mouse liver
GSM8114827
mouse liver fibrotic liver disease 43 MB 3,064 obs silver H&E
TechnologyVisium
Organismmouse
Tissueliver
Conditionfibrotic liver disease
Obs3,064
silver H&E
Cite this collection
No linked publication found — please cite the data source.