Functional Heterogeneity of Mouse Prostate Stromal Cells Revealed by Single-Cell RNA-Seq

We perform a single-cell RNA sequencing analysis to investigate the phenotypic and functional heterogeneity of the adult mouse prostate stromal cells. Our analysis identifies three major cell populations representing the smooth muscle cells and two types of fibroblast cells enriched by Sca-1 and CD90. The Sca-1⁺CD90⁺ fibroblast cells are in direct contact with the epithelial cells and express growth factors and genes associated with cell motility, developmental process, and androgen biosynthesis. This suggests that they may regulate epithelial cell survival and growth. The Sca-1⁺CD90^-/low myofibroblast-like cells highly express genes associated with the extracellular matrix and cytokine-mediated signaling pathways, indicating a role in tissue repair and immune responses. The Sca-1⁺CD90^-/low cells significantly suppress the capacity of the basal cells for bipotent differentiation in the prostate organoid assay. Collectively, we identify the surface markers enabling physical separation of stromal subpopulations and generate the gene expression profiles implying their cellular functions.