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Castration-Insensitive Luminal Cells of the Proximal Prostate are Urethral in Origin
46 Pages Posted: 21 Apr 2020 Publication Status: Review Complete
More...Abstract
Castration-insensitive epithelial progenitors capable of regenerating the prostate have been a subject of extensive research. These cells are proposed to be concentrated in the proximal region of the prostate based on facultative assays. Identification of facultative prostate progenitor cells by single cell surface markers has precluded a definitive characterization of this cell type and delayed a consensus on the identity of the prostate progenitor. Here, we use single cell RNA sequencing (scRNA-seq) to obtain a complete transcriptomic profile of all mouse prostate epithelial cells to objectively identify cellular sub-types in the prostate. These data reveal that previously identified facultative progenitors marked by TROP2, Sca-1, KRT4, and PSCA are actually luminal epithelia of the urethra that extend into the proximal prostate and are resistant to castration-induced androgen deprivation. Mouse urethral cells were identified to be the equivalent of previously identified human urethral cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an ‘embryonic reawakening’, but the cellular origin of the hyperplastic growth concentrated in the peri-urethral region is unclear. We demonstrate an increase in urethral luminal epithelia within glandular nodules from patients with BPH. Urethral cells are further increased in patients treated with a 5 alpha reductase inhibitors. Together, our data demonstrate that the putative prostate progenitors enriched by castration in the proximal prostate are urethral luminal epithelia and that these cells may play an important role in the etiology of human BPH.
Keywords: Prostate, progenitor, castration, urethra, single cell RNA sequencing, BPH
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