A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors
- Columbia University Medical Center, United States
- Weill Cornell Medical Center, United States
Abstract
Understanding the cellular constituents of the prostate is essential for identifying the cell of origin for prostate adenocarcinoma. Here we describe a comprehensive single-cell atlas of the adult mouse prostate epithelium, which displays extensive heterogeneity. We observe distal lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV), a proximally-enriched luminal population (LumP) that is not lobe-specific, and a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about anatomical relationships between the mouse and human prostate.
Data availability
Single-cell RNA-sequencing data from this study have been deposited in the Gene Expression Omnibus (GEO) under the accession number GSE150692, and can also be accessed through the Broad Institute Single-Cell Portal (www.singlecell.broadinstitute.org).
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Single-cell RNA-seq analysis of mouse and human prostateNCBI Gene Expression Omnibus, GSE150692.
Article and author information
Author details
Funding
National Cancer Institute (R01CA238005)
- Michael M Shen
National Cancer Institute (U54CA193313)
- Raul Rabadan
- Michael M Shen
National Cancer Institute (P50CA211024)
- Massimo Loda
- Michael M Shen
National Cancer Institute (K99CA194287)
- Maho Shibata
T.J. Martell Foundation
- Michael M Shen
Department of Defense Prostate Cancer Research Program (W81XWH-18-1-0424)
- Francesco Cambuli
National Science Foundation
- Laura Crowley
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal studies were conducted according to protocols (AC-AABE0556, AC-AABG0564, AC-AABE5557) approved by the Columbia University Irving Medical Center (CUIMC) Institutional Animal Care and Use Committee (IACUC).
Human subjects: Human prostate tissue specimens were obtained from patients undergoing cystoprostatectomy for bladder cancer or radical prostatectomy at Columbia University Irving Medical Center or at Weill Cornell Medicine. Patients gave informed consent under an Institutional Review Board-approved protocol (AAAN8850).
Copyright
© 2020, Crowley et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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