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Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury super

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

ORGANISM(S): Mus musculus

PROVIDER: GSE261721 | GEO | 2024/03/15

REPOSITORIES: GEO

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Transcriptional Dynamics of Hepatic Sinusoid-Associated Cells After Liver Injury.

Project description:Background and aimsHepatic sinusoidal cells are known actors in the fibrogenic response to injury. Activated hepatic stellate cells (HSCs), liver sinusoidal endothelial cells, and Kupffer cells are responsible for sinusoidal capillarization and perisinusoidal matrix deposition, impairing vascular exchange and heightening the risk of advanced fibrosis. While the overall pathogenesis is well understood, functional relations between cellular transitions during fibrogenesis are only beginning to be resolved. At single-cell resolution, we here explored the heterogeneity of individual cell types and dissected their transitions and crosstalk during fibrogenesis.Approach and resultsWe applied single-cell transcriptomics to map the heterogeneity of sinusoid-associated cells in healthy and injured livers and reconstructed the single-lineage HSC trajectory from pericyte to myofibroblast. Stratifying each sinusoidal cell population by activation state, we projected shifts in sinusoidal communication upon injury. Weighted gene correlation network analysis of the HSC trajectory led to the identification of core genes whose expression proved highly predictive of advanced fibrosis in patients with nonalcoholic steatohepatitis (NASH). Among the core members of the injury-repressed gene module, we identified plasmalemma vesicle-associated protein (PLVAP) as a protein amply expressed by mouse and human HSCs. PLVAP expression was suppressed in activated HSCs upon injury and may hence define hitherto unknown roles for HSCs in the regulation of microcirculatory exchange and its breakdown in chronic liver disease.ConclusionsOur study offers a single-cell resolved account of drug-induced injury of the mammalian liver and identifies key genes that may serve important roles in sinusoidal integrity and as markers of advanced fibrosis in human NASH.

| S-EPMC7820956 | biostudies-literature

Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury super

Project description:Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury super

| PRJNA1088486 | ENA

Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury [scRNA-seq]

Project description:Here we profile the transcripts of app. 35.000 single cells isolated from livers of healthy and diseased mice. We show the transcriptomic change associated with fibrosis induction in the non-parenchymal cell types (hepatic stellate cells, liver endothelial cells and macrophages). We reveal a hitherto unknown feature of the HSCs otherwise functionally attributed to the LECs.

2020-08-25 | GSE145086 | GEO

Transcriptional Dynamics of Hepatic Sinusoid-Associated Cells After Liver Injury [bulk RNA-seq]

2024-03-16 | GSE261720 | GEO

Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury [scRNA-seq]

Project description:Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury [scRNA-seq]

| PRJNA605984 | ENA

Transcriptional Dynamics of Hepatic Sinusoid-Associated Cells After Liver Injury [bulk RNA-seq]

Project description:Transcriptional Dynamics of Hepatic Sinusoid-Associated Cells After Liver Injury [bulk RNA-seq]

| PRJNA1088489 | ENA

Hepatic p53 protein level governs liver s sensitivity to drug-induced liver injury

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-05-31 | GSE155696 | GEO

Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem.

Project description:Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus. However, the construction of hepatic sinusoids has always been a challenge for liver chips, especially for large-scale liver microsystems. Herein, we report an approach for the construction of hepatic sinusoids. In this approach, hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply. Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed. Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids, cell viability is witnessed to be considerably high, liver microstructure formation occurs, and hepatocyte metabolism is enhanced. In addition, this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing. This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.

| S-EPMC10247758 | biostudies-literature

Drug-induced liver injury

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-01-22 | E-GEOD-54257 | biostudies-arrayexpress

Transcriptional dynamics of hepatic stellate cells in experimental acute liver injury, liver fibrosis and liver fibrosis reversal.

Project description:Transcriptional alterations during different stages of hepatic stellate cell activation were determined using RNA Sequencing. Models include acute liver injury (1 injection of CCl4) and chronic liver injury (8 injections of CCl4 over 4-week period) with different recovery timepoints. Illumina NextSeq 500 High was used for sequencing.

2021-12-15 | GSE176042 | GEO

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