Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

We performed transcriptomic studies comparing phenotypically defined PMSCs (PDGFRa/CD34/CD9high:CD200low) to HSCs (Vitamin-A fluorescent) of high purity, using bulk RNAseq. We further extended bulk RNAseq analyses of the two cell populations to myofibroblasts derived from both cell types in culture, including an early and late stage of differentiation for PMSC-MFs. Comparative analyses of gene expression indicated that 100 genes in PMSCs and 112 genes in HSCs, i) were overexpressed according to both scRNAseq and bulk RNAseq analyses, and ii) remained differentially expressed in these cells throughout their myofibroblastic differentiation. We selected the most differentially expressed of these genes, to build a multigene expression signature of PMSCs/PMSC-MFs (7 genes) and of HSCs/HSC-MFs (6 genes). mRNA profiles of PMSCs (n=4) and HSCs (n=4), and their derived myofibroblasts in culture, including PMSC-MFs-3d (n=4), PMSC-MFs-7d (n=4) and HSC-MFs-3d (n=4).