Initiation of hepatic stellate cell activation extends into chronic liver disease

Author:

De Smet Vincent,Eysackers Nathalie,Merens Vincent,Kazemzadeh Dastjerd MinaORCID,Halder Georg,Verhulst StefaanORCID,Mannaerts IngeORCID,van Grunsven Leo A.ORCID

Abstract

AbstractActivated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.

Funder

Fonds Wetenschappelijk Onderzoek

Bijzonder Onderzoeksfonds

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

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