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Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling



During wound healing, stem cells provide functional mature cells to meet acute demands for tissue regeneration1. Simultaneously, the tissue must maintain a pool of stem cells to sustain its future regeneration capability. However, how these requirements are balanced in response to injury is unknown. Here we demonstrate that after wounding or ultraviolet type B irradiation, melanocyte stem cells (McSCs) in the hair follicle2 exit the stem cell niche before their initial cell division, potentially depleting the pool of these cells. We also found that McSCs migrate to the epidermis in a melanocortin 1 receptor (Mc1r)-dependent manner and differentiate into functional epidermal melanocytes, providing a pigmented protective barrier against ultraviolet irradiation over the damaged skin. These findings provide an example in which stem cell differentiation due to injury takes precedence over stem cell maintenance and show the potential for developing therapies for skin pigmentation disorders by manipulating McSCs.

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Figure 1: McSCs migrate from the hair follicle niche to the epidermis in response to injury or UVB irradiation.
Figure 2: McSCs migrate directly from the hair follicle niche to the epidermis without proliferation.
Figure 3: McSCs in Mc1r mutant mice show defects in migration to the epidermis.
Figure 4: Epidermal melanocytes reconstitute McSCs in de novo hair follicles formed in the wound.

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Follicle-derived epidermal melanocytes were initially observed at G. Cotsarelis' laboratory at the University of Pennsylvania, and this work benefited greatly from the mentorship and generosity of G. Cotsarelis. We thank P. Manga at New York University (NYU) for valuable discussion and for providing melan-a cells and antibody to mouse tyrosinase. We thank E. Hernando's lab at NYU for the protocol of the melanocyte migration assay. We thank the Microscopy Core of NYU for use of confocal microscopes (NCRRS10 RR023704-01A1). M.T. is supported by the NYU Kimmel Stem Cell Center and NYSTEM training grant C026880. M.I. is supported by US National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 1R01AR059768-01A1 and the Ellison Medical Foundation.

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W.C.C. performed experiments, interpreted data and wrote the manuscript. M.T., P.R., H.H., W.L. and Y.R.C. performed experiments and interpreted data. J.C. provided human skin and interpreted data. P.O. generated Trp2-lacZ mice and interpreted the data. M.I. performed experiments, interpreted data and wrote the manuscript.

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Correspondence to Mayumi Ito.

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The authors declare no competing financial interests.

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Chou, W., Takeo, M., Rabbani, P. et al. Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat Med 19, 924–929 (2013).

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