Ferguson Blake, Kunisada Takahiro, Aoki Hitomi, Handoko Herlina Y, Walker Graeme J
QIMR Berghofer Medical Research Institute, Herston, 4006, Qld, Australia.
Photochem Photobiol Sci. 2015 Jun;14(6):1179-89. doi: 10.1039/c5pp00098j.
Melanocyte stem cells (MCSCs) in the upper portion of the hair follicle periodically supply melanocytes (MCs) that migrate downward into the hair bulb during anagen, the growth phase of the hair cycle. However MCs can also migrate upwards. We previously observed an increase in epidermal MC density in the mouse epidermis after a single ultraviolet radiation (UVR) exposure in neonatal, but not adult mice. To better understand MCSC activation by UVR we methodically studied the response of MCs to narrow band UVB (since UVA does not invoke this response) exposure in neonatal mice, and in adults at different stages of the hair cycle. We found that a single exposure of adult mice did not induce activation of MCSCs, in any stage of the hair cycle. When adult mice MCSCs were isolated in telogen, multiple UVB exposures resulted in their activation and production of daughter cells, which migrated upwards to the epidermis. Importantly, the MCSCs produced new progeny without themselves having incurred DNA damage after UVB exposure. This, together with examination of MC localisation in the skin of mice overexpressing stem cell factor in their keratinocytes, leads us to conclude that MCSC activation by UVB is driven via paracrine production of either SCF and/or other keratinocyte cytokines. We re-examined the increase in epidermal MC density in neonatal mouse skin. This effect was much more profound after only a single exposure than that of even multiple exposures to adult skin, and we show that in this setting also, the epidermal MCs mostly derive from activation of MC precursors in the upper hair follicle, and most likely via a cell extrinsic mechanism. Hence, although adaptive changes in the skin induced by repetitive UVB exposures are necessary in adult mice, in both the adult and neonatal context the division and migration upwards of follicular MCSCs is the major mode by which epidermal MC numbers increase after UVR exposure.
毛囊上部的黑素细胞干细胞（MCSCs）会定期供应黑素细胞（MCs），这些黑素细胞在毛发生长周期的生长期（即生长期）向下迁移至毛球。然而，黑素细胞也可以向上迁移。我们之前观察到，新生小鼠而非成年小鼠在单次紫外线辐射（UVR）暴露后，其表皮中的黑素细胞密度会增加。为了更好地理解紫外线辐射对黑素细胞干细胞的激活作用，我们系统地研究了新生小鼠以及处于毛发生长周期不同阶段的成年小鼠的黑素细胞对窄谱中波紫外线（由于长波紫外线不会引发这种反应）暴露的反应。我们发现，成年小鼠在毛发生长周期的任何阶段进行单次暴露都不会诱导黑素细胞干细胞的激活。当处于休止期的成年小鼠黑素细胞干细胞被分离出来时，多次中波紫外线暴露会导致它们激活并产生子代细胞，这些子代细胞向上迁移至表皮。重要的是，黑素细胞干细胞在中波紫外线暴露后产生了新的后代，而自身并未发生DNA损伤。这一点，再加上对在角质形成细胞中过表达干细胞因子的小鼠皮肤中黑素细胞定位的研究，使我们得出结论，中波紫外线对黑素细胞干细胞的激活是通过旁分泌产生干细胞因子和/或其他角质形成细胞细胞因子来驱动的。我们重新审视了新生小鼠皮肤中表皮黑素细胞密度的增加情况。这种效应在单次暴露后比成年皮肤即使多次暴露后的效应要深刻得多，并且我们表明，在这种情况下，表皮黑素细胞也大多源自毛囊上部黑素细胞前体的激活，很可能是通过一种细胞外机制。因此，尽管成年小鼠需要重复中波紫外线暴露诱导皮肤发生适应性变化，但在成年和新生情况下，毛囊黑素细胞干细胞的分裂和向上迁移都是紫外线辐射暴露后表皮黑素细胞数量增加的主要方式。
