The adult hair follicle: cradle for pluripotent neural crest stem cells.
The adult hair follicle: cradle for pluripotent neural crest stem cells.
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DOI：
10.1002/bdrc.20008
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发表时间：
2004-06-01
期刊：
影响因子：
--
通讯作者：
Grim, Milos
中科院分区：
文献类型：
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作者：
Sieber-Blum, Maya;Grim, Milos
本文综述了最近在成年哺乳动物毛囊中发现的两种新的神经嵴源性细胞：多能干细胞和默克尔细胞。Wnt 1-cre/R26 R复合转基因小鼠，其在外周表达β-半乳糖苷酶的神经嵴特异性的方式，被用来跟踪神经嵴细胞。神经嵴细胞早在胚胎第9.5天就侵入面部表皮。神经嵴来源的细胞沿着胡须毛囊的整个范围存在。这包括凸起区域，角质形成细胞干细胞的表皮生态位，以及毛囊底部的基质。我们已经确定，在体外克隆分析，成年胡须毛囊的隆起区含有多能神经嵴干细胞。在培养中，β-半乳糖苷酶阳性细胞从隆突外植体中迁移，将其鉴定为神经嵴来源的细胞。当这些细胞在克隆培养物中重悬和生长时，它们产生含有多种分化细胞类型的集落，包括神经元、许旺细胞、平滑肌细胞、色素细胞、软骨细胞和可能的其他类型的细胞。这一结果为克隆形成细胞的多能性提供了证据。连续克隆显示，隆突来源的神经嵴细胞进行自我更新，这将其鉴定为干细胞。多能神经嵴细胞也位于成年小鼠的背部皮肤毛发中。胡须毛囊的隆起区域被许多默克尔细胞包围，这些细胞与支配神经末梢一起形成缓慢适应的机械感受器，维持稳定的皮肤凹陷。默克尔细胞在双转基因小鼠中表达β-半乳糖苷酶，这证实了它们的神经嵴起源。总之，我们的数据表明，成人毛囊的表皮含有多能神经嵴干细胞，称为表皮神经嵴干细胞（eNCSC），和一个新发现的神经嵴衍生物，默克尔细胞。eNCSC固有的高度可塑性以及它们在皮肤中容易接近的事实使它们成为多种自体细胞治疗策略的有吸引力的候选者。
This review focuses on the recent identification of two novel neural crest-derived cells in the adult mammalian hair follicle, pluripotent stem cells, and Merkel cells. Wnt1-cre/R26R compound transgenic mice, which in the periphery express beta-galactosidase in a neural crest-specific manner, were used to trace neural crest cells. Neural crest cells invade the facial epidermis as early as embryonic day 9.5. Neural crest-derived cells are present along the entire extent of the whisker follicle. This includes the bulge area, an epidermal niche for keratinocyte stem cells, as well as the matrix at the base of the hair follicle. We have determined by in vitro clonal analysis that the bulge area of the adult whisker follicle contains pluripotent neural crest stem cells. In culture, beta-galactosidase-positive cells emigrate from bulge explants, identifying them as neural crest-derived cells. When these cells are resuspended and grown in clonal culture, they give rise to colonies that contain multiple differentiated cell types, including neurons, Schwann cells, smooth muscle cells, pigment cells, chondrocytes, and possibly other types of cells. This result provides evidence for the pluripotentiality of the clone-forming cell. Serial cloning showed that bulge-derived neural crest cells undergo self-renewal, which identifies them as stem cells. Pluripotent neural crest cells are also localized in the back skin hair of adult mice. The bulge area of the whisker follicle is surrounded by numerous Merkel cells, which together with innervating nerve endings form slowly adapting mechanoreceptors that transduce steady skin indentation. Merkel cells express beta-galactosidase in double transgenic mice, which confirms their neural crest origin. Taken together, our data indicate that the epidermis of the adult hair follicle contains pluripotent neural crest stem cells, termed epidermal neural crest stem cells (eNCSCs), and one newly identified neural crest derivative, the Merkel cell. The intrinsic high degree of plasticity of eNCSCs and the fact that they are easily accessible in the skin make them attractive candidates for diverse autologous cell therapy strategies.