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Originally published in Science Express on 23 December 2004
Science 4 February 2005:
Vol. 307. no. 5710, pp. 720 - 724
DOI: 10.1126/science.1099593
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Reports

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

Emi K. Nishimura,1*{dagger} Scott R. Granter,2 David E. Fisher1*

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.

1 Department of Pediatric Hematology/Oncology, Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

{dagger} Address after 9 February 2005: Department of Dermatology, Hokkaido University Graduate School of Medicine, N15, W7, Sapporo 060-8638, Japan.

* To whom correspondence should be addressed. E-mail: emi_k_nishimura{at}yahoo.co.jp (E.K.N.); David_Fisher{at}dfci.harvard.edu (D.E.F.)

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