Stress and stem cells.
Stress and stem cells.
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DOI：
10.1002/wdev.56
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发表时间：
2012-11
影响因子：
--
通讯作者：
Tower, John
中科院分区：
文献类型：
--
作者：
Tower, John
干细胞的独特性质和功能使它们特别容易受到压力的影响，也导致它们受到压力的调节。干细胞分裂必须响应在正常组织周转期间补充细胞的需求以及响应损伤。氧化应激、机械应激、生长因子和细胞因子是干细胞分裂和分化的信号。许多调节干细胞自我更新和分化的保守途径也是应激反应途径。干细胞的长寿命和分裂潜力产生转化（癌症）的倾向，并且特定的应激反应如细胞凋亡和衰老作为抗肿瘤机制。由CDK抑制剂调节的静止和由FOXO转录因子调节的低氧生态位功能可以减少几种类型干细胞的压力，以促进长期维持。衰老是干细胞的一个特别相关的压力，因为在整个生命周期中对干细胞功能的重复需求可能会产生累积的细胞自主效应，包括表观遗传失调，突变和端粒侵蚀。此外，生物体的老化损害干细胞生态位和系统信号的功能，包括慢性炎症和氧化应激。
The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress.