1. Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA

Correspondence to: Wei-Qiang Gao¹ Correspondence and requests for materials should be addressed to W.-Q.G. (Email: gao@gene.com).

The existence of prostate stem cells (PSCs) was first postulated from the observation that normal prostate regeneration can occur after repeated cycles of androgen deprivation and replacement in rodents¹. Given the critical role of PSCs in maintaining prostate tissue integrity and their potential involvement in prostate tumorigenesis², it is important to define specific markers for normal PSCs. Several cell-surface markers have been reported to identify candidate PSCs, including stem cell antigen-1 (Sca-1, also known as Ly6a), CD133 (Prom1) and CD44 (refs 3—10). However, many non-PSCs in the mouse prostate also express these markers and thus identification of a more defined PSC population remains elusive. Here we identify CD117 (c-kit, stem cell factor receptor) as a new marker of a rare adult mouse PSC population, and demonstrate that a single stem cell defined by the phenotype Lin^-Sca-1⁺CD133⁺CD44⁺CD117⁺ can generate a prostate after transplantation in vivo. CD117 expression is predominantly localized to the region of the mouse prostate proximal to the urethra and is upregulated after castration-induced prostate involution—two characteristics consistent with that of a PSC marker. CD117⁺ PSCs can generate functional, secretion-producing prostates when transplanted in vivo. Moreover, CD117⁺ PSCs have long-term self-renewal capacity, as evidenced by serial isolation and transplantation in vivo. Our data establish that single cells in the adult mouse prostate with multipotent, self-renewal capacity are defined by a Lin^-Sca-1⁺CD133⁺CD44⁺CD117⁺ phenotype.

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