Amoh Yasuyuki, Li Lingna, Katsuoka Kensei, Penman Sheldon, Hoffman Robert M
AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA.
Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5530-4. doi: 10.1073/pnas.0501263102. Epub 2005 Mar 31.
We have recently shown that the expression of nestin, the neural stem cell marker protein, is expressed in bulge-area stem cells of the hair follicle. We used transgenic mice with GFP expression driven by the nestin regulatory element [nestin-driven GFP (ND-GFP)]. The ND-GFP stem cells give rise to the outer-root sheath of the hair follicle as well as an ND-GFP interfollicular vascular network. In this study, we demonstrate that ND-GFP stem cells isolated from the hair-follicle bulge area that are negative for the keratinocyte marker keratin 15 can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. These pluripotent ND-GFP stem cells are positive for the stem cell marker CD34, as well as keratin 15-negative, suggesting their relatively undifferentiated state. The apparent primitive state of the ND-GFP stem cells is compatible with their pluripotency. Furthermore, we show that cells derived from ND-GFP stem cells can differentiate into neurons after transplantation to the subcutis of nude mice. These results suggest that hair-follicle bulge-area ND-GFP stem cells may provide an accessible, autologous source of undifferentiated multipotent stem cells for therapeutic application.
我们最近发现，神经干细胞标志物蛋白巢蛋白在毛囊隆突区干细胞中表达。我们使用了由巢蛋白调控元件驱动绿色荧光蛋白表达的转基因小鼠[巢蛋白驱动的绿色荧光蛋白（ND-GFP）]。ND-GFP干细胞可形成毛囊的外根鞘以及ND-GFP毛囊间血管网络。在本研究中，我们证明，从毛囊隆突区分离出的、对角质形成细胞标志物角蛋白15呈阴性的ND-GFP干细胞在体外可分化为神经元、神经胶质细胞、角质形成细胞、平滑肌细胞和黑素细胞。这些多能性ND-GFP干细胞对干细胞标志物CD34呈阳性，对角蛋白15呈阴性，表明它们处于相对未分化状态。ND-GFP干细胞明显的原始状态与其多能性相符。此外，我们还表明，源自ND-GFP干细胞的细胞在移植到裸鼠皮下后可分化为神经元。这些结果表明，毛囊隆突区ND-GFP干细胞可能为治疗应用提供一种可获取的、自体的未分化多能干细胞来源。
