Generation of a prostate from a single adult stem cell
Generation of a prostate from a single adult stem cell
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DOI：
10.1038/nature07427
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发表时间：
2008-12-11
期刊：
影响因子：
64.8
通讯作者：
Gao, Wei-Qiang
中科院分区：
文献类型：
--
作者：
Leong, Kevin G.;Wang, Bu-Er;Gao, Wei-Qiang
前列腺干细胞(PSCs)的存在首先是因为观察到，在反复的雄激素剥夺和替代周期后，啮齿动物可以发生正常的前列腺再生[1]。鉴于PSCs在维持前列腺组织完整性方面的关键作用及其在前列腺癌发生中的潜在作用，为正常PSCs定义特定的标记物是很重要的。一些细胞表面标记已被报道用于识别候选PSCs，包括干细胞抗原-1(SCA-1，又称Ly6a)、CD133(Prom1)和CD44(参考文献3-10)。然而，许多小鼠前列腺中的非PSC也表达这些标记，因此更明确的PSC群体的鉴定仍然难以捉摸。在这里，我们发现CD117(c-kit，干细胞因子受体)是一种罕见的成年小鼠PSC群体的新标志物，并证明了由表型LIN(-)SCA-1(+)CD133(+)CD44(+)CD117(+)定义的单个干细胞可以在体内移植后产生前列腺。CD117的表达主要定位于小鼠前列腺靠近尿道处的区域，并在去势诱导的前列腺退缩后上调-这两个特征与PSC标记一致。CD117(+)PSCs在体内移植后可以产生功能正常、分泌能力强的前列腺。此外，CD117(+)PSCs具有长期的自我更新能力，体内连续分离和移植证明了这一点。我们的数据表明，成年小鼠前列腺中具有多潜能、自我更新能力的单个细胞是由LIN(-)SCA-1(+)CD133(+)CD44(+)CD117(+)表型定义的。
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 rodents(1). Given the critical role of PSCs in maintaining prostate tissue integrity and their potential involvement in prostate tumorigenesis(2), 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.