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Identification of portal mesenchymal stem cells and derived myofibroblasts in liver fibrosis

Abstract : Previous work has demonstrated that portal myofibroblasts (PMFs) significantly contributed to liver fibrogenesis and modulated angiogenesis in liver fibrosis. The main aim of this thesis was to elucidate the landscape of portal mesenchymal cells, with a particular focus on a portal mesenchymal stem cell niche. We characterized the murine normal liver portal mesenchymal cell landscape. Importantly, we revealed a portal mesenchymal cell population with the features of mesenchymal stem cells (MSCs), designated portal mesenchymal stem cells (PMSCs) that possessed the ability to give rise to PMFs in vitro. Furthermore, we identified Slit2 as a new marker of PMSCs based on scRNA-seq and bulk RNA-seq analysis. In vivo, we observed PMSC expansion (measured by the expression of Slit2) in liver from both animal fibrosis models (DDC and CDAA) and patients with chronic liver disease (NASH, PSC and other liver disease). Notably, we defined the specific gene signatures for PMSCs and hepatic stellate cells (HSCs), respectively. By using these markers, we provide further evidence indicating that PMSCs expand in correlation with fibrogenesis and angiogenesis in different murine and human liver diseases, whereas the HSCs gene signatures did not vary. In conclusion, our work collectively offers insights into the components and functions of the mammalian liver portal mesenchymal cell populations, and in particular, identify and characterize PMSCs and their derived myofibroblasts, opening up the possibility for the development of novel targeted drugs or biomarkers of clinical significance with increased precision.
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Submitted on : Monday, September 26, 2022 - 9:52:14 AM
Last modification on : Tuesday, October 18, 2022 - 4:31:21 AM

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  • HAL Id : tel-03787910, version 1

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Lin Lei. Identification of portal mesenchymal stem cells and derived myofibroblasts in liver fibrosis. Cellular Biology. Sorbonne Université, 2020. English. ⟨NNT : 2020SORUS099⟩. ⟨tel-03787910⟩

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