title: Keratinocyte stem cells but not melanocyte stem cells are the primary target for radiation-induced hair graying.
abstract: Ionizing radiation (IR)-induced hair graying is caused by the ectopic differentiation of melanocyte stem cells (MSCs) in their niche located at the bulge region of the hair follicle. Keratinocyte stem cells (KSCs) in the bulge region are an important component of that niche. However, little is known about the relationship between MSC differentiation and the KSC niche during IR-induced hair graying. We found that both follicular MSCs and KSCs were affected by IR by using immunohistochemical detection of γH2AX as a genotoxicity marker. We also found that KSCs prepared from irradiated mice were functionally affected by IR as indicated by their reduced colony-forming activity in culture and the delayed hair cycle in vivo. However, these effects of IR on KSCs were temporal. The MSC population, which proliferated and differentiated to melanocytes, was persistently maintained after irradiation. In addition to the loss of colony-forming activity, irradiated keratinocytes including KSCs suppressed the colony formation of MSCs in vitro. Furthermore, pigmented hairs were not reconstituted in vivo in the presence of irradiated KSCs or keratinocytes. These results provide a previously unreported insight that the primary target of IR during the induction of hair graying is follicular KSCs rather than MSCs.
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Aoki
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Motohashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000528:radiation effects*; D000818:Animals; D002454:Cell Differentiation / Q000528:radiation effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004249:DNA Damage / Q000528:radiation effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000528:radiation effects; D006200:Hair Color / Q000528:radiation effects*; D018859:Hair Follicle / Q000166:cytology / Q000528:radiation effects; D015603:Keratinocytes / Q000166:cytology / Q000528:radiation effects*; D007763:Lac Operon; D008544:Melanocytes / Q000166:cytology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012038:Regeneration / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000379:methods*