title: Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment.
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 P63(CreERT2), 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.
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hamana
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Junchen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Wenzhou Medical College, Wenzhou, 325030 Zhejiang, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030; Xiamen Zhongshan Hospital, Xiamen, 361004 Fujian, China.
authors.forename: Pan
authors.initials: P
authors.lastname: You
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Julia Y F
authors.initials: JYF
authors.lastname: Chang
authors.affiliation: Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Wallace L
authors.initials: WL
authors.lastname: McKeehan
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030; Wenzhou Medical College, Wenzhou, 325030 Zhejiang, China; Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas 77807. Electronic address: fwang@ibt.tamhsc.edu.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000032:analysis*; D011467:Prostate / Q000166:cytology*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis; D018874:Spheroids, Cellular; D015534:Trans-Activators / Q000032:analysis*; D014157:Transcription Factors / Q000032:analysis
chemical_list: D018398:Homeodomain Proteins; C493597:Lgr5 protein, mouse; C102837:Nkx3-1 protein, mouse; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse
keywords: cell signaling; fibroblast growth factor (FGF); fibroblast growth factor receptor (FGFR); prostate; stem cells