Mechanisms of Hair Graying: Incomplete Melanocyte Stem Cell Maintenance in the Niche

Emi K. Nishimura,^1* Scott R. Granter,² David E. Fisher^1*

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.

头发变白是人类年老的一个重要标志，然而目前这个机制还不明确，我们使用黑色素转基因小鼠和老化的人的毛囊来研究头发变白是由黑色素干细胞缺乏自我更新能力。而缺乏Bcl2可以促进头发变白的过程，Bcl2缺乏可以导致选择性的黑色素干细胞的凋亡，而不是由于黑色素细胞分化。而且生理性的黑色素干细胞的老化与异位黑色素沉着或者是分化有关，而这一过程可以由黑色素细胞转录调节因子Mitf的突变所促进。