A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin
A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin
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DOI：
10.1634/stemcells.2007-0281
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Chandran, Siddharthan
中科院分区：
文献类型：
--
作者：
Hunt, David P. J.;Morris, Paul N.;Chandran, Siddharthan
皮肤来源的前体细胞（SKPs）是多能神经嵴相关干细胞，其作为自我更新球体生长并且能够产生神经元和髓鞘形成胶质细胞。SKPs具有临床意义，因为它们是可接近的并且可能是自体的。然而，尽管球体可以容易地从胚胎和新生儿皮肤中分离，但SKP频率在成年期急剧福尔斯，并且从成年人皮肤产生的初级球体更成问题。此外，培养起始细胞群是不确定的和异质的，限制了解决这些细胞的重要方面的实验研究，如内源性前体在体内的行为和神经生成的分子机制。使用相结合的命运映射和显微解剖的方法，我们确定并表征了一个高度富集的生态位的神经嵴来源的球体形成细胞内的真皮乳头的毛囊成人皮肤。我们证明，与整个面部皮肤相比，啮齿动物触须毛囊的毛乳头富集了1,000倍的球形神经嵴衍生细胞。这些“乳头状球体”具有与SKPs相似的表型和发育特征，可以容易地在体外扩增，并且能够响应于适当的提示产生神经元和神经胶质细胞。我们证明，乳头状球可以有效地产生和扩大从成人面部皮肤显微解剖一个单一的毛囊。这种靶向高度富集的球体形成细胞的小生境的策略提供了一种新颖且有效的方法，用于从可获得的成体体细胞来源产生神经元和神经胶质细胞，该方法既明确又微创。
Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic. In addition, the culture-initiating cell population is undefined and heterogeneous, limiting experimental studies addressing important aspects of these cells such as the behavior of endogenous precursors in vivo and the molecular mechanisms of neural generation. Using a combined fate-mapping and microdissection approach, we identified and characterized a highly enriched niche of neural crest-derived sphere-forming cells within the dermal papilla of the hair follicle of adult skin. We demonstrated that the dermal papilla of the rodent vibrissal follicle is 1,000-fold enriched for sphere-forming neural crest-derived cells compared with whole facial skin. These "papillaspheres" share a phenotypic and developmental profile similar to that of SKPs, can be readily expanded in vitro, and are able to generate both neuronal and glial cells in response to appropriate cues. We demonstrate that papillaspheres can be efficiently generated and expanded from adult human facial skin by microdissection of a single hair follicle. This strategy of targeting a highly enriched niche of sphere-forming cells provides a novel and efficient method for generating neuronal and glial cells from an accessible adult somatic source that is both defined and minimally invasive.