Urethral luminal epithelia are castration‐insensitive cells of the proximal prostate

Background Castration‐insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has fai...

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Bibliographic Details
Published in:The Prostate Vol. 80; no. 11; pp. 872 - 884
Main Authors: Joseph, Diya B., Henry, Gervaise H., Malewska, Alicia, Iqbal, Nida S., Ruetten, Hannah M., Turco, Anne E., Abler, Lisa L., Sandhu, Simran K., Cadena, Mark T., Malladi, Venkat S., Reese, Jeffrey C., Mauck, Ryan J., Gahan, Jeffrey C., Hutchinson, Ryan C., Roehrborn, Claus G., Baker, Linda A., Vezina, Chad M., Strand, Douglas W.
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01.08.2020
Subjects:
Adolescent
Adult
Animals
Antigens, Neoplasm - metabolism
benign prostatic hyperplasia
Castration
Cell Adhesion Molecules - metabolism
Cell surface
Embryos
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - metabolism
Etiology
Flow cytometry
Humans
Hyperplasia
Male
Mice
Mice, Inbred C57BL
Nodules
Prostate
Prostate - cytology
Prostate - metabolism
prostate stem cell
prostatic urethra
Reductase
Ribonucleic acid
RNA
single‐cell RNA sequencing
Stem Cells - cytology
Stem Cells - metabolism
Surface markers
Transcription
Transcriptomics
Urethra
Urethra - cytology
Urethra - metabolism
Young Adult
single-cell RNA sequencing
prostatic urethra
prostate stem cell
castration
benign prostatic hyperplasia
ISSN:0270-4137, 1097-0045, 1097-0045
Online Access:Get full text
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Summary:Background Castration‐insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. Methods Here, we use single‐cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan‐transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. Results Our data reveal that previously identified facultative progenitors marked by Trop2, Sca‐1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration‐induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock 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 periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5‐α reductase inhibitor. Conclusions Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.
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ISSN:0270-4137
1097-0045
1097-0045
DOI:10.1002/pros.24020