Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche
Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche
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DOI：
10.1126/science.1099593
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发表时间：
2005-02-04
期刊：
影响因子：
56.9
通讯作者：
Fisher, DE
中科院分区：
文献类型：
--
作者：
Nishimura, EK;Granter, SR;Fisher, DE
头发变白是人类衰老最明显的标志，但其机制在很大程度上尚不清楚。在这里，我们使用黑素细胞标记的转基因小鼠和老化的人类毛囊来证明头发变白是由黑素细胞干细胞的自我维持缺陷引起的。这一过程在Bcl 2缺乏的情况下显著加速，Bcl 2缺乏导致黑素细胞干细胞的选择性凋亡，而不是分化的黑素细胞在进入休眠状态时在小生境内的选择性凋亡。此外，黑素细胞干细胞的生理老化与异位色素沉着或分化内的小生境，一个过程加速了黑素细胞主转录调节Mitf突变。
Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator Mitf.