PMID- 23549419 OWN - NLM STAT- MEDLINE DCOM- 20131031 LR - 20181202 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 133 IP - 9 DP - 2013 Sep TI - Keratinocyte stem cells but not melanocyte stem cells are the primary target for radiation-induced hair graying. PG - 2143-51 LID - 10.1038/jid.2013.155 [doi] AB - 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 gammaH2AX 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. FAU - Aoki, Hitomi AU - Aoki H AD - Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu, Japan. FAU - Hara, Akira AU - Hara A FAU - Motohashi, Tsutomu AU - Motohashi T FAU - Kunisada, Takahiro AU - Kunisada T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130402 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 SB - IM MH - Adult Stem Cells/cytology/*radiation effects MH - Animals MH - Cell Differentiation/radiation effects MH - Cells, Cultured MH - Coculture Techniques MH - DNA Damage/radiation effects MH - Epidermal Cells MH - Epidermis/radiation effects MH - Hair Color/*radiation effects MH - Hair Follicle/cytology/radiation effects MH - Keratinocytes/cytology/*radiation effects MH - Lac Operon MH - Melanocytes/cytology/*radiation effects MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Regeneration/radiation effects MH - Whole-Body Irradiation/*methods EDAT- 2013/04/04 06:00 MHDA- 2013/11/01 06:00 CRDT- 2013/04/04 06:00 PHST- 2012/11/20 00:00 [received] PHST- 2013/02/27 00:00 [revised] PHST- 2013/03/10 00:00 [accepted] PHST- 2013/04/04 06:00 [entrez] PHST- 2013/04/04 06:00 [pubmed] PHST- 2013/11/01 06:00 [medline] AID - S0022-202X(15)36411-3 [pii] AID - 10.1038/jid.2013.155 [doi] PST - ppublish SO - J Invest Dermatol. 2013 Sep;133(9):2143-51. doi: 10.1038/jid.2013.155. Epub 2013 Apr 2.