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

Science
Authors
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-cell RNA sequencing, we identified a rare luminal population in the mouse prostate that expresses stemlike genes ( and ) and a large population of differentiated cells (, ). 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.

Year of Publication
2020
Journal
Science
Volume
368
Issue
6490
Pages
497-505
Date Published
2020 05 01
ISSN
1095-9203
DOI
10.1126/science.aay0267
PubMed ID
32355025
Links
Grant list
R01 CA193837 / CA / NCI NIH HHS / United States
U54 CA224079 / CA / NCI NIH HHS / United States
R01 CA155169 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA180922 / CA / NCI NIH HHS / United States
R33 CA202820 / CA / NCI NIH HHS / United States