Expression profiling in hiPSC-derived liver sinusoidal endothelial cells and hepatic stellate cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE92771 | GEO | 2017/07/27
SECONDARY ACCESSION(S): PRJNA358579
REPOSITORIES: GEO
Similar Datasets
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.
2016-03-02 | E-GEOD-68000 | biostudies-arrayexpress
Project description:We have established culture systems to generate liver progenitor cells (LPCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs) from hiPSCs. Then, we established co-culture system of hiPSC-derived liver cells and performed RNA-seq of hiPSC-derived liver model.
2017-07-27 | GSE98710 | GEO
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).
2016-03-02 | GSE68000 | GEO
Project description:The human liver contains multiple cell types whose epigenetic patterns are undetermined. We examined the promoter methylome of purified and uncultured hepatic stellate cells (HSCs), hepatocytes (HEPs) and liver sinusoidal endothelial cells (LSECs), by methylated DNA immunoprecipitation (MeDIP) and array hybridization. Uncultured HSCs, LSECs and Heps show ~7000-8000 methylated promoters, with 60-70% similarity between all cell types. GO analysis for commonly methylated genes reveals involvement in germ cell development, segregating germ-line from somatic lineage methylation. HSCs, LSECs and HEPs also contain ~500-1000 uniquely methylated promoters; these are implicated in signaling and biosynthetic processes (HSCs), lipid transport and metabolism (LSECs), and chromatin assembly (HEPs). The promoter methylome of culture-activated HSCs deviates from that of their uncultured (quiescent) counterparts. HSC culture-induced activation also enhances methylation differences between individual donors; however this does not necessarily relate to changes in gene expression. HSc activation results in a net gain of promoter DNA methylation, despite the demethylation and de novo methylation of thousands of promoters. Our data provide to our knowledge the first genome-wide maps of promoter DNA methylation in human purified and uncultured liver cell types. Although methylation profiles are largely similar between HSCs, LSECs and hepatocytes, the detection of cell type-specific methylation patterns suggests a differential epigenetic programming of these cell types in the liver. Determine the promoter DNA methylation pattern of 3 uncultured, reshly isolated, human healthy liver cell types (hepatocytes (HEPs), liver sinusoidal endothelial cells (LSECs) and haptic stellate cells (HSCs), and of HSCs after a 24-h culture-induced activation.
2015-12-21 | E-GEOD-66796 | biostudies-arrayexpress
Project description:The human liver contains multiple cell types whose epigenetic patterns are undetermined. We examined the promoter methylome of purified and uncultured hepatic stellate cells (HSCs), hepatocytes (HEPs) and liver sinusoidal endothelial cells (LSECs), by methylated DNA immunoprecipitation (MeDIP) and array hybridization. Uncultured HSCs, LSECs and Heps show ~7000-8000 methylated promoters, with 60-70% similarity between all cell types. GO analysis for commonly methylated genes reveals involvement in germ cell development, segregating germ-line from somatic lineage methylation. HSCs, LSECs and HEPs also contain ~500-1000 uniquely methylated promoters; these are implicated in signaling and biosynthetic processes (HSCs), lipid transport and metabolism (LSECs), and chromatin assembly (HEPs). The promoter methylome of culture-activated HSCs deviates from that of their uncultured (quiescent) counterparts. HSC culture-induced activation also enhances methylation differences between individual donors; however this does not necessarily relate to changes in gene expression. HSc activation results in a net gain of promoter DNA methylation, despite the demethylation and de novo methylation of thousands of promoters. Our data provide to our knowledge the first genome-wide maps of promoter DNA methylation in human purified and uncultured liver cell types. Although methylation profiles are largely similar between HSCs, LSECs and hepatocytes, the detection of cell type-specific methylation patterns suggests a differential epigenetic programming of these cell types in the liver.
2015-12-21 | GSE66796 | GEO
Project description:Unveiling the regulatory pathways maintaining hepatic stellate cells (HSC) in a quiescent (q) phenotype is essential to develop new therapeutic strategies to treat fibrogenic diseases. To uncover the miRNA-mRNAs regulatory interactions in qHSCs, HSCs were FACS-sorted from healthy livers and activated HSCs were generated in vitro. MiRNA Taqman array analysis showed HSCs expressed a low number of miRNA, from which 46 were down-regulated and 212 up-regulated upon activation. Computational integration of miRNA and gene expression profiles revealed that 66% of qHSCs miRNAs correlated with more than 6 altered targeted mRNAs (17,28±10,7 targets/miRNA), whereas aHSC-associated miRNAs had an average of 1,49 targeted genes. Interestingly, interaction networks generated by miRNA-targeted genes in qHSCs were associated with key HSCs activation processes. Next, selected miRNAs were validated in healthy and cirrhotic human livers and miR-192 was chosen for functional analysis. Down-regulation of miR-192 in HSC was found to be an early event during fibrosis progression in mouse models of liver injury. Moreover, mimic assays for miR-192 in HSCs revealed its role in HSC activation, proliferation and migration. Together, these results uncover the importance of miRNAs in the maintenance of qHSC phenotype and form the basis for understanding the regulatory networks in HSCs. Transcriptomic profile derived from four quiescent hepatic stellate (QHSC), four activated hepatic stellate (AHSC), three liver sinusoidal endothelial (LSEC) and two hepatocytes cells (HEP).
2015-11-23 | E-GEOD-67664 | biostudies-arrayexpress
Project description:We utilized RNA-sequencing strategy to explore the characterstics of gene expression profile of LSECs during CCl4-fibrosis, and to compare the activation feature between fibrotic-LSECs and fibrotic-HSCs which are the most acknowledged gatekeepers holding the key to liver fibrogenesis.
2020-04-01 | GSE120281 | GEO
Project description:Hepatic stellate cells (HSCs) play a central role in the progression of liver fibrosis by producing extracellular matrices. The development of drugs to suppress liver fibrosis has been hampered by the lack of human quiescent HSCs (qHSCs) and an appropriate in vitro model that faithfully recapitulates HSC activation. In the present study, we developed a culture system to generate qHSC-like cells from human-induced pluripotent stem cells (hiPSCs) that can be converted into activated HSCs in culture. To monitor the activation process, a red fluorescent protein (RFP) gene was inserted in hiPSCs downstream of the activation marker gene actin alpha 2 smooth muscle (ACTA2). Using qHSC-like cells derived from RFP-reporter iPSCs, we screened a repurposing chemical library and identified therapeutic candidates that prevent liver fibrosis. Hence, hiPSC-derived qHSC-like cells will be a useful tool to study the mechanism of HSC activation and to identify therapeutic agents.
2021-12-02 | GSE155017 | GEO
Project description:Normal and cirrhotic LSECs can influence hepatic stellate cells (HSCs) differently. This project aims to determine the set of proteins secreted by LSECs from healthy and cirrhotic livers, and identify the protein(s) that promote HSC activation.
2018-11-06 | PXD009010 | Pride
Project description:Activation and migration of hepatic stellate cells (HSCs) followed by matrix deposition are characteristics of liver fibrosis. Several studies have shown the importance of hepatocyte and endothelial cell-derived extracellular vesicles (EVs) in liver pathobiology. However, less is known about the role of HSC-derived EVs in liver diseases. In this study, we investigated the molecules released through HSC-derived EVs and whether these can promote fibrosis.
2018-10-18 | PXD007258 | Pride