Single-cell transcriptomics enable uncovering portal mesenchymal stem cells as precursors of myofibroblasts in liver fibrosis [bulk RNA-seq]

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 (Figure 5C). 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 (9 genes).