title: Coupling of the radiosensitivity of melanocyte stem cells to their dormancy during the hair cycle.
abstract: Current studies have revealed that stem cells are more radiosensitive than mature cells. As somatic stem cells are mostly kept in a quiescent state, this conflicts with Bergonié and Tribondeau's law that actively mitotic cells are the most radiosensitive. In this study, we focused on hair graying to understand the stress-resistance of melanocyte stem cells (McSCs). We used Dct-H2B-GFP transgenic mice which enables the stable visualization of McSCs and an anti-Kit monoclonal antibody which selectively eradicates amplifying McSCs. The results demonstrate that quiescent McSCs are rather radiosensitive, but the coexistence of non-quiescent McSCs provides the stem cell pool with radioresistance. The irradiated quiescent McSCs prematurely differentiate in the niche upon their activation without sufficiently renewing themselves for cyclic hair pigmentation. These data indicate that tissue radiosensitivity is largely dependent on the state of somatic stem cells under their local microenvironment.
authors.affiliation: Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan; Department of Dermatology, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Aoto
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mohri
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yokozeki
authors.forename: Emi K
authors.initials: EK
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D018859:Hair Follicle / Q000378:metabolism* / Q000473:pathology; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010858:Pigmentation / Q000235:genetics / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects*; D055153:Stem Cell Niche / Q000235:genetics / Q000528:radiation effects*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014965:X-Rays
keywords: DNA damage; Kit; cell cycle; hair follicles; ionizing radiation; melanocyte stem cell; quiescence