<p>Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. To understand the cell-of-origin for human prostate ancer (PCa), we first need to dissect the lineage hierarchy within prostatic epithelium. By describing a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing (Nat Commun, 2016), we show that basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal gene-expression profile is enriched in advanced, anaplastic, castration-resistant prostate cancers (CRPC), suggesting a potential basal cell-of-origin for these aggressive types of PCa. To further understand the luminal cell lineage hierarchy which is heavily understudied in the field, we have developed an in vitro culture system that allows the enrichment of luminal progenitors (LPs) from freshly purified bulk human prostatic luminal cells. Functionally, we demonstrate that human LPs could serve as a cell-of-origin for human PCa (Stem Cells Transl Med, 2017). Study of LPs i</p>