Nature 456, 804-808 (11 December 2008) | doi:10.1038/nature07427; Received 25 January 2008; Accepted 16 September 2008; Published online 22 October 2008

Generation of a prostate from a single adult stem cell

Kevin G. Leong1, Bu-Er Wang1, Leisa Johnson1 & Wei-Qiang Gao1

  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.