存在于小鼠皮肤中特定小环境中的表皮干细胞,可以确保皮肤的动态平衡得到高效维持。毛囊隆突中的干细胞负责毛囊再生和伤口愈合。它们产生一组异质性细胞——比如说这些细胞在其对内部和外部提示的反应能力方面就是异质性的。
由Salvador Benitah及其同事进行的这项研究表明,生物钟通过调控毛囊隆突干细胞对其微环境的反应能力来控制它们的激发状态和异质性。这意味着,始终都会有一组“准备好了”的细胞来对激发刺激做出反应,同时防止该微环境内的所有干细胞都变得具有响应能力。表皮干细胞若受到扰动,会影响组织的长期平衡,并使组织容易生成肿瘤。(生物谷Bioon.com)
>>延伸阅读:J. Cell. Biochem.:人类毛囊干细胞可修复神经
>>延伸阅读:Nature:毛囊干细胞与毛发再生
>>延伸阅读:研究证明毛囊中全能角化细胞是真正的干细胞
>>延伸阅读:Science:法国科学家发现生物钟的调节新机制
>>延伸阅读:Nature:康奈尔大学确定生物钟蛋白的结构
>>延伸阅读:哺乳动物和果蝇有相同的生物钟基因
doi:10.1038/nature10649
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The circadian molecular clock creates epidermal stem cell heterogeneity
Peggy Janich, Gloria Pascual, Anna Merlos-Suárez, Eduard Batlle, Jürgen Ripperger, Urs Albrecht, Hai-Ying M. Cheng, Karl Obrietan, Luciano Di Croce & Salvador Aznar Benitah
Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.