Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Profiling of the transcriptome during culture-induced activation of rat hepatic stellate cells.

ABSTRACT: Gene expression was determined in primary rat hepatic stellate cells during the in vitro activation process in freshly isolated (4h), quiescent (1d), early activated (3d) and fully activated (7d) hepatic stellate cells. The cells were isolated from the liver using density centrifugation and cultured on plastic in DMEM containing serum for the indicated time. RNA was isolated using the Qiagen Rneasy Mini Kit. The Affymetrix Gene Chip Rat Gene 2.0 ST was used for gene expression analysis performed by the genomic core facility of the EMBL (Heidelberg, Germany). All experiments were performed three times with independent animals.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Eva Schumacher

PROVIDER: E-MTAB-5404 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Combined Methylome and Transcriptome Analysis During Rat Hepatic Stellate Cell Activation.

Schumacher Eva Christine EC Götze Silke S Kordes Claus C Benes Vladimir V Häussinger Dieter D

Stem cells and development 20171128 24

Hepatic stellate cells (HSCs) are mesenchymal stem cells (MSCs) of the liver. They are unique among MSCs, since HSCs remain in a quiescent, retinoid-storing state in the normal liver but become activated after liver injury and contribute to tissue repair. The epigenetic mechanisms accompanying the transition of HSCs from a quiescent to an activated state are in the focus of the present study. We investigated the methylome and transcriptome during this process and observed profound changes. While ...[more]

PMID: 29054136

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Project description:Background & Aims: Rapid induction of beta-PDGF receptor (beta-PDGFR) is a core feature of hepatic stellate cell activation, the hallmark of liver fibrogenesis. However, biological consequences of the induction are not well characterized. We aimed to determine the involvement of beta-PDGFR-mediated molecular pathway activation on hepatic stellate cells in liver injury, fibrogenesis, and carcinogenesis in vivo. Methods: Loss and constitutive activation of beta-PDGFR were assessed in mouse models with either a stellate cell-specific beta-PDGFR knockout or the expression of an autoactivating mutation respectively. Liver injury and fibrosis were induced in two mechanistically distinct models: carbontetrachloride (CCl4) treatment and ligation of the common bile duct. Hepatocarcinogenesis with underlying liver injury/fibrosis was assessed by a single dose of diethylnitrosamine (DEN) followed by repeated injections of CCl4. Genome-wide expression profiling was performed isolated stellate cells from these models to determine deregulated pathways. Results: Depletion of beta-PDGFR in hepatic stellate cells led to decreased histological liver injury, serum transaminases, collagen alpha 1(I) and alpha smooth muscle actin expression, and collagen deposition. Stellate cell proliferation was significantly reduced after acute hepatic injury in vivo. In contrast, autoactivation of beta-PDGFR in stellate cells accelerated liver fibrosis, most prominently after 6 weeks of CCl4 induced injury. There was no difference in development of DEN-induced pre-neoplastic loci according to the status of beta-PDGFR. Conclusions: Depletion of beta-PDGFR in hepatic stellate cells attenuated the development of liver injury, fibrosis, and stellate cell proliferation in multiple animal models, whereas the constitutive activation of beta-PDGFR enhanced fibrosis. However, manipulation of beta-PDGFR alone did not reduce development of dysplastic nodules. These findings indicate that titration of receptor beta-PDGFR expression on stellate cells parallels fibrosis and injury, but may not impact the development of hepatic neoplasia alone. Hepatic stellate cells were isolated from liver of beta-PDGFR-wild-type or knockout mice, and treated with beta-PDGF ligand or vehicle control.

Dataset Information

Profiling of the transcriptome during culture-induced activation of rat hepatic stellate cells.

Publications

Combined Methylome and Transcriptome Analysis During Rat Hepatic Stellate Cell Activation.

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