A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors
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).
-
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.
Reviewing Editor
- Nima Sharifi, Cleveland Clinic, United States
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).
Version history
- Received: May 29, 2020
- Accepted: September 10, 2020
- Accepted Manuscript published: September 11, 2020 (version 1)
- Version of Record published: October 1, 2020 (version 2)
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.
Metrics
-
- 8,978
- views
-
- 1,149
- downloads
-
- 71
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cancer Biology
- Cell Biology
Establishing a zebrafish model of a deadly type of brain tumor highlights the role of the immune system in the early stages of the disease.
-
- Cancer Biology
The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.