在压力下对抗性干细胞的命运决定了白发和黑色素瘤之间的决定
Yasuaki Mohri1, Jialiang Nie1, Hironobu Morinaga2
1Division of Aging and Regeneration, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nature cell biology
|October 6, 2025
概括
环境暴露会影响健康,影响衰老和癌症. 这项研究揭示了黑色素细胞干细胞如何应对基因毒性损伤,影响头发变白和黑色素瘤风险.
科学领域:
- 干细胞生物学 干细胞生物学
- 衰老的研究研究.
- 环境健康 环境健康
背景情况:
- 暴露组,包括终身环境暴露,显著影响健康结果.
- 衰老的特点是体质组织的功能衰退,导致像发和癌症这样的表型.
- 精确的基因毒素,信号通路和驱动这些衰老表型的细胞机制尚未完全理解.
研究的目的:
- 阐明细胞机制,其中黑色素细胞干细胞 (McSCs) 和它们的利基相互作用,以确定干细胞命运,以应对基因毒性压力.
- 研究不同类型的基因毒性损伤如何影响McSC行为,并导致老化表型和癌症风险.
主要方法:
- 用于McSC命运跟踪的小鼠模型.
- 分析了细胞衰老合差异化 (seno-差异化) 途径.
- 研究了DNA双链断裂和致癌物暴露的作用.
- 检查了干细胞利基中的阿拉基酸代谢和KIT连接体信号传递.
主要成果:
- DNA 双链断裂诱导McSC 胸部分化,导致McSC 枯竭,头发变灰,并保护黑色素瘤.
- 致癌物质可以通过激活阿拉基酸代谢和KIT配体来抑制McSC的脑内分化,从而促进McSC的自我更新.
- 麦克SC命运 (自我更新与耗尽) 是通过利基互动和累积的基因毒性侮辱来动态调节的.
结论:
- 黑色素细胞干细胞的命运是由干细胞利基内的应激反应,对抗性途径决定的.
- 由环境暴露所调节的McSC扩张和耗尽之间的平衡,极大地影响着老化表型和癌症易感性.
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