Kitl induction in postnatal and adult mice induces epidermal pigmentation via activation of melanocyte stem cells

Summary: Abstract Body: Melanocytes (Mcs) determine the color of hair and skin, and their abnormalities cause gray hair, vitiligo, and pigment spots. White hair of receptor tyrosine kinase Kit loss-of-function mutant mice reflects Kit dependency of Mc development. Inversely, overexpression of Kitl, a ligand for Kit, in the epidermis promotes the proliferation and differentiation of developing melanoblasts (Mbs) and maintains Mcs throughout life in the epidermis, where Mcs are not maintained in wild-type mice. Therefore, Kitl-Kit signaling is expected to also be involved in the maintenance of adult melanocyte stem cells (MSCs). Administration of the Kit function-blocking antibody Ack2 ablatesproliferating Mbs, however, quiescent MSCs present in the bulge region of hair follicles are resistant to ACK2 and are maintained independently of Kit signaling. Thus, the exact role of Kit signaling in adult MSCs remains to be further tested. To investigate the impact of Kitl expression in postnatal or adult Mcs, we generated genetically modified mice expressing the Kitl transgene throughout the body in a doxycycline-dependent manner. Doxycycline administration stimulated growth and differentiation of postnatal or adult MSCs. We also generated mice that can transiently induce Kit1 expression only in the epidermis. Even a single pulse expression of Kitl only in the epidermis had long-term effects on MSCs, resulting in pigmentation of the entire epidermis. Intermittent induction of Kitl repeatedly induced pigmented skin. Conditional Kitl overexpression also rescued radiation-induced hair graying in adults. These results indicate that regulation of Kitl signaling is crucial for MSC homeostasis and Mc cell differentiation in postnatal and adult stages. Hitomi Aoki¹ 1. Stem Cell and Regenerative Medicine, Gifu Daigaku, Gifu, Gifu Prefecture, Japan. Pigmentation, Melanoma, and Melanoma Immune Surveillance