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

Area of Science:

• Urology
• Stem Cell Biology
• Regenerative Medicine

Background:

• The adult prostate exhibits notable regenerative capabilities, making it a valuable model for studying adult stem cell biology.
• Identifying specific stem cell populations is crucial for understanding tissue repair and disease progression in the prostate.

Purpose of the Study:

• To identify and characterize prostate epithelial progenitor cells.
• To investigate the role of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) in prostate regeneration and castration resistance.

Main Methods:

• Utilized genetic lineage tracing to track Lgr5-expressing cells and their progeny.
• Performed renal transplantation assays with single Lgr5(+) cells to assess their regenerative potential.
• Employed Lgr5(+) cell depletion to determine their necessity in prostate regeneration.

Main Results:

• Identified Lgr5 expression in a rare population of prostate epithelial progenitor cells.
• Discovered a castration-resistant Lgr5(+) cell population in regressed prostate tissue, primarily luminal.
• Demonstrated that Lgr5(+) cells are long-lived and essential for prostatic regeneration, with both luminal and basal Lgr5(+) cells expanding upon regeneration.
• Showed that single Lgr5(+) cells can generate multilineage prostatic structures.

Conclusions:

• Lgr5 marks a rare population of adult prostate stem cells.
• Lgr5(+) cells are essential for the regenerative capacity of the castrated adult prostate.
• These findings provide insights into the cellular hierarchy and regenerative mechanisms within the prostate.