Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment

Area of Science:

• Urology
• Stem Cell Biology
• Prostate Cancer Research

Background:

• Prostate stem cells (P-SCs) generate all prostate epithelial cell types.
• Previous studies suggested P-SCs exist in the luminal compartment.
• The lineage of prostasphere-forming cells remained undetermined.

Purpose of the Study:

• To identify and characterize the specific location and lineage of prostate stem cells.
• To determine the hierarchical relationship between different prostate stem cell populations.
• To understand the potential of P-SCs in prostate development and cancer.

Main Methods:

• Lineage tracing using P63(CreERT2) in mouse models.
• Analysis of prostasphere and organoid cultures.
• Expression analysis of cell type-specific markers.

Main Results:

• Sphere-forming P-SCs express P63 and reside in the basal compartment, designated as basal P-SCs (P-bSCs).
• P-bSCs differentiate into luminal organoid cells (AR(+) and CK18(+)) but cannot form spheres.
• Prostaspheres contain quiescent stem cells, indicating P-bSCs are early in the stem cell hierarchy.

Conclusions:

• Basal P-SCs (P-bSCs) are identified as key stem cells early in the prostate hierarchy.
• Understanding P-bSCs may offer new strategies for controlling prostate cancer progression and relapse.
• Further research into P-SC contributions to prostate development and cancer is warranted.