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Published Online December 23, 2004
Science DOI: 10.1126/science.1099593

Reports

Submitted on April 26, 2004
Accepted on December 8, 2004

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

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

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 & Women's Hospital, Harvard Medical School, Boston, MA, USA.

* To whom correspondence should be addressed.
Emi K. Nishimura , E-mail: emi_k_nishimura{at}yahoo.co.jp
David E. Fisher , E-mail: David_Fisher{at}dfci.harvard.edu

Hair graying is the most obvious sign of aging in man, yet its mechanism is largely unknown. Here we utilize 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 within the niche at their entry into the dormant state, but not of differentiated melanocytes. 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.


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