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

Stem Cell Reports. 2015 May 12;4(5):768-79. doi: 10.1016/j.stemcr.2015.04.003. Epub 2015 Apr 30.

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.

MeSH terms

  • Androgens / pharmacology
  • Animals
  • Cell Lineage
  • Cells, Cultured
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Nude
  • Orchiectomy
  • Prostate / cytology
  • Prostate / metabolism*
  • Prostate / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / metabolism*
  • Regeneration / drug effects
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Testosterone / pharmacology

Substances

  • Androgens
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Testosterone