Castration-resistant Lgr5(+) cells are long-lived stem cells required for prostatic regeneration.
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.
Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Bu-er
BE
Wang
Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Xi
X
Wang
Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Jason E
JE
Long
Center for Advanced Light Microscopy, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Jeff
J
Eastham-Anderson
Department of Pathology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Ron
R
Firestein
Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: junttila.melissa@gene.com.
Melissa R
MR
Junttila
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009919:Orchiectomy; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D013739:Testosterone