基因毒性压力通过触发它们的分化,取消了黑色素细胞干细胞的更新
Ken Inomata1, Takahiro Aoto, Nguyen Thanh Binh
1Division of Stem Cell Medicine, Center for Cancer and Stem Cell Research, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan.
Cell
|June 16, 2009
概括
通过耗尽黑色素细胞干细胞 (MSCs),DNA损伤导致头发变白. DNA损伤反应触发了MSC分化,而不是细胞灭绝,ATM激酶作为关键的干性检查点.
科学领域:
- 干细胞生物学 干细胞生物学
- 衰老的研究研究.
- 对DNA损伤的反应反应
背景情况:
- 身体干细胞枯竭和DNA损伤积累与衰老的表型有关.
- 白发,衰老的标志,结果是受损的黑色素细胞干细胞 (MSC) 维护.
研究的目的:
- 调查不可弥补的DNA损伤对MSC更新的影响.
- 阐明DNA损伤影响MSC和头发白化的机制.
- 为了确定ATAXIA-telangiectasia突变 (ATM) 激酶在MSC维护中的作用.
主要方法:
- 在小鼠模型中使用电离辐射诱导不可挽回的DNA损伤.
- 对MSC行为,分化,亡和衰老的分析.
- 评估头发变白的表型.
- 基因操纵来研究ATM激酶缺乏的作用.
主要成果:
- 在小鼠中,不可挽回的DNA损伤取消了MSC的更新.
- DNA损伤反应诱导MSC分化成成熟的黑色素细胞,而不是亡或衰老.
- MSC的消耗导致不可逆转的头发变白.
- 由于ATM激酶缺乏,MSC对子宫外分化的敏感性增加,突出了其作为干性检查点的作用.
结论:
- 无法弥补的DNA损伤会触发MSCs的过早分化,导致它们的枯竭和头发变白.
- 通过防止子宫外分化,ATM激酶对于维持MSC的质量和数量至关重要,作为茎状检查点.
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