Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons
Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons
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DOI：
10.1073/pnas.0501263102
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发表时间：
2005-04-12
影响因子：
11.1
通讯作者：
Hoffman, RM
中科院分区：
文献类型：
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作者：
Amoh, Y;Li, L;Hoffman, RM
我们最近发现，神经干细胞标记蛋白巢蛋白的表达，在毛囊的隆起区干细胞中表达。我们使用了由巢蛋白调控元件驱动的GFP表达的转基因小鼠[巢蛋白驱动的GFP（ND-GFP）]。ND-GFP干细胞产生毛囊的外根鞘以及ND-GFP毛囊间血管网络。在这项研究中，我们证明，ND-GFP干细胞分离的毛囊隆起区，是阴性的角质形成细胞标记角蛋白15可以分化成神经元，神经胶质细胞，角质形成细胞，平滑肌细胞，和黑色素细胞在体外。这些多能ND-GFP干细胞对干细胞标志物CD 34呈阳性，角蛋白15呈阴性，表明它们处于相对未分化状态。ND-GFP干细胞的表观原始状态与其多能性相容。此外，我们表明，来源于ND-GFP干细胞的细胞移植到裸鼠皮下后可以分化为神经元。这些结果表明，毛囊隆起区ND-GFP干细胞可能提供一个可访问的，自体来源的未分化的多能干细胞的治疗应用。
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.