昼夜分子钟创造了表皮干细胞的异质性
Peggy Janich1, Gloria Pascual, Anna Merlos-Suárez
1Center for Genomic Regulation and UPF, 08003 Barcelona, Spain.
Nature
|November 15, 2011
概括
昼夜时钟调节了表皮干细胞的激活. 破坏这种时钟会导致干细胞失衡,导致过早衰老和瘤发育的改变.
科学领域:
- 干细胞生物学 干细胞生物学
- 时间生物学 时间生物学
- 皮肤病学 皮肤病学
背景情况:
- 鼠表皮干细胞表现出休眠和激活的循环,用于组织更新.
- 干细胞激活是异质的,细胞处于不同的响应状态.
- 毛囊干细胞的毛囊干细胞以相反的昼夜阶段的细胞为庇护.
研究的目的:
- 调查昼夜时钟在调节表皮干细胞异质性和对恒温信号的反应中的作用.
- 确定核心时钟蛋白如何影响干细胞激活状态.
- 评估昼夜时钟中断对表皮平衡和瘤产生的影响.
主要方法:
- 使用昼夜时钟记者鼠标模型.
- 分析了毛囊的干细胞种群.
- 通过核心时钟蛋白Bmal1.1.的基因表达调制进行了研究.
- 删除Bmal1 (Arntl) 或Per1/2基因的研究效应.
主要成果:
- 在休眠的利基中,在相反的昼夜阶段共存的干细胞种群被确定.
- Bmal1表达波动,创造了易受影响或不太容易激活的种群.
- 删除Bmal1或Per1/2分别导致干细胞积累或耗尽.
- 循环节的干扰导致皮肤过早衰老,并减少了状瘤的发展.
结论:
- 昼夜时钟精确地控制了表皮干细胞的时间行为.
- 昼夜时钟的扰乱会破坏干细胞平衡.
- 循环时钟平衡对于调节瘤发生倾向至关重要.
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