Division of Endocrinology, Department of Medicine, School of Medicine, University of California, Irvine, CA, USA.
Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA.
Stem Cells. 2023 Apr 25;41(4):319-327. doi: 10.1093/stmcls/sxad013.
First described in the early 20th century, diurnal oscillations in stem cell proliferation exist in multiple internal epithelia, including in the gastrointestinal tract, and in the epidermis. In the mouse epidermis, 3- to 4-fold more stem cells are in S-phase during the night than during the day. More recent work showed that an intact circadian clock intrinsic to keratinocytes is required for these oscillations in epidermal stem cell proliferation. The circadian clock also regulates DNA excision repair and DNA damage in epidermal stem cells in response to ultraviolet B radiation. During skin inflammation, epidermal stem cell proliferation is increased and diurnal oscillations are suspended. Here we discuss possible reasons for the evolution of this stem cell phenomenon. We argue that the circadian clock coordinates intermediary metabolism and the cell cycle in epidermal stem cells to minimize the accumulation of DNA damage from metabolism-generated reactive oxygen species. Circadian disruption, common in modern society, leads to asynchrony between metabolism and the cell cycle, and we speculate this will lead to oxidative DNA damage, dysfunction of epidermal stem cells, and skin aging.
早在 20 世纪初，干细胞增殖的昼夜节律就存在于多种内胚层中，包括胃肠道和表皮。在小鼠表皮中，夜间处于 S 期的干细胞是白天的 3-4 倍。最近的研究表明，角质形成细胞中完整的内在生物钟对于表皮干细胞增殖的这种昼夜节律波动是必需的。生物钟还调节表皮干细胞中的 DNA 切除修复和 DNA 损伤，以响应紫外线 B 辐射。在皮肤炎症期间，表皮干细胞增殖增加，昼夜节律波动暂停。在这里，我们讨论了这种干细胞现象进化的可能原因。我们认为，生物钟协调表皮干细胞中的中间代谢和细胞周期，以最大程度地减少由代谢产生的活性氧引起的 DNA 损伤的积累。现代社会中常见的生物钟紊乱导致代谢和细胞周期之间的失同步，我们推测这将导致氧化 DNA 损伤、表皮干细胞功能障碍和皮肤老化。
