Regenerative potential of prostate luminal cells revealed by single-cell analysis

Wouter R. Karthaus, Matan Hofree, Danielle Choi, Eliot L. Linton, Mesruh Turkekul, Alborz Bejnood, Brett Carver, Anuradha Gopalan, Wassim Abida, Vincent Laudone, Moshe Biton, Ojasvi Chaudhary, Tianhao Xu, Ignas Masilionis, Katia Manova, Linas Mazutis, Dana Pe’er, Aviv Regev*, Charles L. Sawyers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

Androgen deprivation is the cornerstone of prostate cancer treatment. It results in involution of the normal gland to ~90% of its original size because of the loss of luminal cells. The prostate regenerates when androgen is restored, a process postulated to involve stem cells. Using single-cel RNA sequencing, we identified a rare luminal population in the mouse prostate that expresses stemlike genes (Sca1+ and Psca+) and a large population of differentiated cells (Nkx3.1+, Pbsn+). In organoids and in mice, both populations contribute equally to prostate regeneration, partly through androgen-driven expression of growth factors (Nrg2, Rspo3) by mesenchymal cells acting in a paracrine fashion on luminal cells. Analysis of human prostate tissue revealed similar differentiated and stemlike luminal subpopulations that likewise acquire enhanced regenerative potential after androgen ablation. We propose that prostate regeneration is driven by nearly all persisting luminal cells, not just by rare stem cells.

Original languageAmerican English
Pages (from-to)497-505
Number of pages9
JournalScience
Volume368
Issue number6490
DOIs
StatePublished - 1 May 2020
Externally publishedYes

Bibliographical note

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© 2020 American Association for the Advancement of Science. All rights reserved.

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