Prostate sphere-forming stem cells are derived from the P63-expressing basal compartment

Yanqing Huang, Tomoaki Hamana, Junchen Liu, Cong Wang, Lei An, Pan You, Julia Y.F. Chang, Jianming Xu, Wallace L. McKeehan, Fen Wang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, including basal, luminal, and neuroendocrine cells. Multiple methods have been used to identify P-SCs in adult prostates. These include in vivo renal capsule implantation of a single epithelial cell with urogenital mesenchymal cells, in vitro prostasphere and organoid cultures, and lineage tracing with castration-resistant Nkx3.1 expression (CARN), in conjunction with expression of cell type-specific markers. Both organoid culture and CARN tracing show the existence of P-SCs in the luminal compartment. Although prostasphere cells predominantly express basal cell-specific cytokeratin and P63, the lineage of prostasphere-forming cells in the P-SC hierarchy remains to be determined. Using lineage tracing with P63CreERT2, we show here that the sphere-forming P-SCs are P63-expressing cells and reside in the basal compartment. Therefore we designate them as basal P-SCs (P-bSCs). P-bSCs are capable of differentiating into AR+ and CK18+ organoid cells, but organoid cells cannot form spheres. We also report that prostaspheres contain quiescent stem cells. Therefore, the results show that P-bSCs represent stem cells that are early in the hierarchy of overall prostate tissue stem cells. Understanding the contribution of the two types of P-SCs to prostate development and prostate cancer stem cells and how to manipulate them may open new avenues for control of prostate cancer progression and relapse.

Original languageEnglish (US)
Pages (from-to)17745-17752
Number of pages8
JournalJournal of Biological Chemistry
Volume290
Issue number29
DOIs
StatePublished - Jul 17 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Prostate sphere-forming stem cells are derived from the P63-expressing basal compartment'. Together they form a unique fingerprint.

Cite this