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. However, little is known about the relationship between MSC differentiation and keratinocytes during IR-induced hair graying. We investigate the target of IR-induced hair graying.
We found that both follicular MSCs and hair follicle keratinocyte stem cells (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, while these effects were temporal. On the other hand, MSC population, which proliferated and differentiated to mature melanocytes, were persistently maintained after irradiation. In addition, the irradiated keratinocyte lineage cells suppressed the colony formation of MSCs in vitro. Furthermore, in the presence of irradiated keratinocytes, pigmented hairs were not regenerated by using hair reconstitution assay in vivo, while the irradiated MSCs can contribute to the pigmentation of the reconstituted hair.
The severe reduction of MSCs was thus attributed to the temporal loss of the niche activity of KSCs. These results provide a new insight that the primary target of IR sufficient to induce hair graying is not MSCs but follicular KSCs.