Castration-resistant Lgr5+ cells are long-lived stem cells required for prostatic regeneration

Bu-er Wang, Xi Wang, Jason E. Long, Jeff Eastham-Anderson, Ron Firestein, Melissa R. Junttila

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

The adult prostate possesses a significant regenerative capacity that is of great interest for understanding adult stem cell biology. We demonstrate that leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is expressed in a rare population of prostate epithelial progenitor cells, and a castration-resistant Lgr5+ population exists in regressed prostate tissue. Genetic lineage tracing revealed that Lgr5+ cells and their progeny are primarily luminal. Lgr5+ castration-resistant cells are long lived and upon regeneration, both luminal Lgr5+ cells and basal Lgr5+ cells expand. Moreover, single Lgr5+ cells can generate multilineage prostatic structures in renal transplantation assays. Additionally, Lgr5+ cell depletion revealed that the regenerative potential of the castrated adult prostate depends on Lgr5+ cells. Together, these data reveal insights into the cellular hierarchy of castration-resistant Lgr5+ cells, indicate a requirement for Lgr5+ cells during prostatic regeneration, and identify an Lgr5+ adult stem cell population in the prostate.

Original languageEnglish
Pages (from-to)768-779
Number of pages12
JournalStem Cell Reports
Volume4
Issue number5
DOIs
Publication statusPublished - 12 May 2015
Externally publishedYes

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