Single-cell RNA-Seq identifies factors necessary for the regenerative phenotype of prostate luminal epithelial progenitors.

Abstract

Benign prostate hyperplasia and prostate cancer are common diseases that involve the overgrowth of prostatic tissue. Although their pathologies and symptoms differ, both diseases show aberrant activation of prostate progenitor cell phenotypes in a tissue that should be relatively quiescent. This phenomenon prompts a need to better define the normal prostate progenitor cell phenotype and pursue the discovery of causal networks that could yield druggable targets to combat hyperplastic prostate diseases. We used single-cell (sc) RNA-Seq analysis to confirm the identity of a luminal progenitor cell population in both the hormonally intact and castrated mouse prostate. Using marker genes from our scRNA-Seq analysis, we identified factors necessary for the regeneration phenotype of prostate organoids derived from mice and humans in vitro. These data outline potential factors necessary for prostate regeneration and utilization of scRNA-Seq approaches for the identification of pharmacologic strategies targeting critical cell populations that drive prostate disease.