Oral communication, PS3 / C39

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

In vivo responses of melanocyte stem cells and other immature melanocytic cells to ultraviolet radiation-induced damage

BACKGROUND AND OBJECTIVES: The induction of melanoma in mice with neonatal UVR is accompanied by a strong melanocyte (MC) proliferative response. In neonates MCs are in the epidermis but migrating downwards in contact with keratinocytes that are forming the developing hair follicle. After UVR MCs migrate upwards out of the follicular bulge, the location of MC stem cells (MCSCs), again appearing in the interfollicular epidermis a few days later. In adult mice MCSCs are only activated during early anagen. As it is unknown how MCSCs respond to UVR-induced damage, we assessed how they, and other immature bulge MCs, respond by differentiating, proliferating, and migrating to the burned area of skin. METHODS: Neonatal or adult mice were given a single burning UVB exposure and sacrificed at multiple time points afterwards. Skin sections were stained with MC-specific antibodies. We assessed the response of MCSCs to UVR by “isolating” them in vivo in neonates using antibody-mediated depletion of all other MCs, or by exposing adult skin with hair follicles synchronized in telogen. RESULTS: After neonatal UVR MCs increased in number in the epidermis, and in the upper outer root sheath (ORS) of hair follicles (bulge and infundibulum). At least three distinct populations are observed; Kit –ve/Trp1 -ve MCSCs, Kit +ve/Trp1-ve transit amplifying (TA) cells, and fully differentiated Kit +ve/Trp1 +ve MCs. After MC depletion with a Kit-blocking antibody, which removes all MCs except MCSCs, we saw no UVR-induced activation of MCs in the bulge and none in the epidermis. We further tested the response of MCSCs to UVR in adult mice after synchronizing the hair cycle in telogen or anagen, but we could not elicit MC proliferation in the bulge or ORS (at least with a single exposure). UVR treatment of K14-Kitl mice, which have epidermal MCs throughout life, also revealed major differences in UVR responses of neonatal and adult MCs even in the epidermal setting. CONCLUSION: - A single UVR-induced insult to the skin is insufficient to induce MCSC activation in either neonatal or adult mice. - Alternatively, in neonates MCSCs may respond indirectly, requiring the presence of UVR-activated “TA” cells which in turn signal MCSC activation. - As the MC proliferative response does not occur in adult follicles, even in anagen, neonatal MCs must be exquisitely sensitive to this response. - Contact between MCs and keratinocytes is critical to the MC migration.

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