1. Cancer Biology
  2. Stem Cells and Regenerative Medicine
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A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors

  1. Laura Crowley
  2. Francesco Cambuli
  3. Luis Aparicio
  4. Maho Shibata
  5. Brian D Robinson
  6. Shouhong Xuan
  7. Weiping Li
  8. Hanina Hibshoosh
  9. Massimo Loda
  10. Raul Rabadan  Is a corresponding author
  11. Michael M Shen  Is a corresponding author
  1. Columbia University Medical Center, United States
  2. Weill Cornell Medical Center, United States
Research Article
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Cite this article as: eLife 2020;9:e59465 doi: 10.7554/eLife.59465

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.

Article and author information

Author details

  1. Laura Crowley

    Medicine, Genetics and Development, Urology, and Systems Biology, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Francesco Cambuli

    Medicine, Genetics and Development, Urology, and Systems Biology, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8237-7121
  3. Luis Aparicio

    Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Maho Shibata

    Medicine, Genetics and Development, Urology, and Systems Biology, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Brian D Robinson

    Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Shouhong Xuan

    Department of Medicine, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0571-7855
  7. Weiping Li

    Medicine, Genetics and Development, Urology, and Systems Biology, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Hanina Hibshoosh

    Pathology and Cell Biology, Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Massimo Loda

    Department of Pathology and Laboratory Medicin, Weill Cornell Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Raul Rabadan

    Department of Biomedical Informatics and Department of Systems Biology, College of Physicians & Surgeons, Columbia University Medical Center, New York, United States
    For correspondence
    rr2579@cumc.columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
  11. Michael M Shen

    Medicine, Genetics and Development, Urology, and Systems Biology, Columbia University Medical Center, New York, United States
    For correspondence
    mshen@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4042-1657

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).

Reviewing Editor

  1. Nima Sharifi, Cleveland Clinic, United States

Publication history

  1. Received: May 29, 2020
  2. Accepted: September 10, 2020
  3. Accepted Manuscript published: September 11, 2020 (version 1)

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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