RNA-sequencing-based comparative analysis of human hepatic progenitor cells and their niche from alcoholic steatohepatitis livers

基于 RNA 测序的酒精性脂肪性肝炎肝脏中人类肝祖细胞及其微环境的比较分析

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作者:An Ceulemans, Stefaan Verhulst, Matthias Van Haele, Olivier Govaere, Juan-Jose Ventura, Leo A van Grunsven, Tania Roskams

Methods

side population (SP), epithelial cell adhesion molecule (EpCAM) and trophoblast antigen 2 (TROP-2) membrane marker isolation and laser capture microdissection. Gene expression profiles of fluorescent-activated cell-sorted HPCs, whole liver extracts and laser microdissected HPC niches were determined by RNA-sequencing. Immunohistochemical evaluation of the isolated populations indicated the enrichment of HPCs in the SP, EpCAM+ and TROP-2+ cell populations. Pathway analysis of the transcription profiles of human HPCs showed an enrichment and activation of known HPC pathways like Wnt/β-catenin, TWEAK and HGF. Integration of the HPC niche profile suggests autocrine signalling by HPCs (TNFα, PDGFB and VEGFA) as well as paracrine signalling from the surrounding niche cells including MIF and IGF-1. In addition, we identified IL-17 A signalling as a potentially novel pathway in HPC biology. In

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