Early Mouse Hepatic Stellate Cell Activation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51882 | GEO | 2014/01/01
SECONDARY ACCESSION(S): PRJNA225669
REPOSITORIES: GEO
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Project description:Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling Transcriptomic profiling of primary human quiescent HSCs (qHSCs), in vitro activated HSCs (aHSCs) and in vitro reverted HSCs (rHSCs). The cell types come from different donors (This is detailed in the original manuscript.).
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Project description:DZNeP is the inhibitor of Ezh2 and paly negative roles on activation of hepatic stellate cells. We used RNA sequencing to identify the effective genes of DZNeP in rat HSCs. The primary rat HSCs was isolated and purified from SD rats, and cultured in DMEM culture medium with 20% FBS for 24 hours. Then the rat HSCs was administrated with DZNeP at 1μM concentration, or with similar volume of DMSO as negative control. 48 hour later, the cells were harvested and cell lysis was subjected to RNA-sequencing. This study identified that DZNeP regulated HSC activation through upregulating the expression of many key anti-fibrotic factors including Tgfβ signaling inhibitor: Bambi; cell cycle inhibitors: p21, Gadd45s; and immunomodulatory cytokine IL10.
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Project description:We identified the genomic characteristics of peritumoral hepatic stellate cells (HSCs) in HBV related HCC. Expression levels of 17160 genes were compared between quiescent and activated HSCs and cancer associated myofibroblasts (CAMFs) from three independent samples per group. We find that among all significant changed genes (≥2-fold change and p<0.05), there were only 188 upregulated and 467 downregulated genes in peritumoral HSCs compared to intratumoral CAMFs. Compared with quiescent HSCs, the same patients-derived culture activated HSCs yielded as many as 1485 upregulated and 1471 downregulated genes. Between peritumoral HSCs/intratumoral CAMFs and culture-activated HSCs , there are 4479 and 3540 upregulated genes, and 3691 and 3380 downregulated genes, respectively. Between peritumoral HSCs/intratumoral CAMFs and quiescent phenotype HSCs, there are 1032 and 994 upregulated genes, and 1654 and 1188 downregulated genes, respectively.
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Project description:The molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. In addition, the gene expression changes associated with activation of primary human hepatic stellate cells, a key event during fibrogenesis, remain poorly characterized. Here, we provide the transriptomic profile underpinning the healthy phenotype of human hepatocytes, liver sinusoidal endothelial cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as activated HSCs (aHSCs) We assess the transcriptome for purified, non-cultured human hepatocytes, liver sinusoidal cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as culture-activated HSCs (aHSCs). Hepatocytes (n=2 donors), LSECs (n=3), qHSCs (n=3) and in vitro activated HSCs (n=3; from the same donors as the qHSCs and LSECs) were used for this study.
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