CUT&Tag analysis of H3K9Me3 binding quiescent and activated primary mouse hepatic stellate cells
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PROVIDER: PRJEB61821 | ENA |
REPOSITORIES: ENA
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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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Project description:Gene expression of mouse hepatic stellate cells was characterized under the following conditions: Quiescent (isolated from normal mouse liver) and reverted (isolated from mouse liver treated with 4 injections of carbontetrachloride followed by 45 day rest period) Affymetrix Mouse 1.0ST gene expression measurements were used to characterize the transcriptomic basis in quiescent hepatic stellate cells, isolated from normal liver, and reverted hepatic stellate cells, isolated from liver treated with 4 injections of CCl4 followed by a 45 day rest period.
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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).
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Project description:Hepatic stellate cells (HSC) constitute the most important fibrogenic cell type during liver fibrosis. To analyse the different phenotypes of quiescent and activated cells, cells of 5 animals were transdifferentiated in a well established in vitro transdifferentiaition assay and compared to freshly seeded, quiescent HSC. Gene expression profiling of quiescent and in vitro activated HSC revealed well known and new marker genes upregulated upon HSC activation. ltbp1 (latent transforming growth factor beta binding protein 1) is a crucial factor controlling the secretion and bioactivation of TGFß1. Using the data comparing quiescent and activated HSC, we were able to qualify the subtle but reproducible differences in gene expression observed when comparing activated ltbp1-deficient and activted wt HSC. ltbp1-deficient HSC showed a less fibrogenic phenotype after 6 days of in vitro transdifferentiation compared to the wt counterparts. The microarray data was indepently confirmed in vivo using an experimental model for the induction of liver fibrosis (ligation of the common bile duct). ltbp1-/- mice, after 4 weeks of bile obstruction, showed markedly reduced signs of liver fibrosis. Keywords: gene expression profiling, analysyis of a fibrogenic cell type in the liver and the influence of ltbp1-k.o.
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