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 stem-like 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 stem-like 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.

Erratum and update (11/13/23):

In the original publication, we incorrectly identified a human immune cell sub-population to be NK cells. This sub-population should instead be annotated as Mast cells. The error does not impact the conclusions of the paper, as no meaningful claims were made about NK cells or mast cells. 

In the published study, cell type annotation was performed by manual cell cluster annotation based on expression of marker genes. Recognizing the limitation of manual annotation, we compared the published annotation with labels generated by two recently published computational labeling tools, CellTypist and Scimilarity. We find that all the remaining manual cell-type annotations reported in the study conformed with those found by automated approaches. The Scimilarity tool identifies a small population of NK cells as well as mast cells. These automated cell-type annotations are now available in the portal.