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Regenerative potential of prostate luminal cells revealed by single-cell analysis
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Regenerative potential of prostate luminal cells revealed by single-cell analysis
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Journal Article
Regenerative potential of prostate luminal cells revealed by single-cell analysis
2020
Overview
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 (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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Androgen Antagonists - therapeutic use
/ Androgen-Binding Protein - genetics
/ Animals
/ Antigens, Neoplasm - genetics
/ Ataxin
/ Cancer
/ Cell Differentiation - genetics
/ GPI-Linked Proteins - genetics
/ Homeodomain Proteins - genetics
/ Humans
/ Male
/ Mesenchymal Stem Cells - physiology
/ Mice
/ Neoplasm Proteins - genetics
/ Nerve Growth Factors - genetics
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - surgery
/ RNA
