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首页> 外文期刊>Journal of Cellular Physiology >The role of oxygen in regulating neural stem cells in development and disease.
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The role of oxygen in regulating neural stem cells in development and disease.

机译：氧气的作用在调节神经干细胞在发展和疾病。

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摘要

Oxygen (O2) is a substrate for energy production in the cell and is a rapid regulator of cellular metabolism. Recent studies have also implicated O2 and its signal transduction pathways in controlling cell proliferation, fate, and morphogenesis during the development of many tissues, including the nervous system. O2 tensions in the intact brain are much lower than in room air, and there is evidence that dynamic control of O2 availability may be a component of the in vivo neural stem cell (NSC) niche. At lower O2 tensions, hypoxia-inducible factor 1alpha (HIF1alpha) facilitates signal transduction pathways that promote self-renewal (e.g., Notch) and inhibits pathways that promote NSC differentiation or apoptosis (e.g., bone morphogenetic proteins). Increasing O2 tension degrades HIF1alpha, thus promoting differentiation or apoptosis of NSCs and progenitors. These dynamic changes in O2 tension can be mimicked to optimize ex vivo production methods for cell replacement therapies. Conversely, disrupted O2 availability may play a critical role in disease states such as stroke or brain tumor progression. Hypoxia during stroke activates precursor proliferation in vivo, while glioblastoma stem cells proliferate maximally in a more hypoxic environment than normal stem cells, which may make them resistant to certain anti-neoplastic therapies. These findings suggest that O2 response is central to the normal architecture and dynamics of NSC regulation and in the etiology and treatment of brain diseases.
机译：氧气(O2)是一个衬底对能源生产在细胞和细胞的快速调节器新陈代谢。O2及其信号转导途径控制细胞增殖,命运,形态发生在许多的发展组织,包括神经系统。完整的大脑远低于的紧张局势房间的空气,有证据表明,动态的控制O2的可用性可能是一个组成部分体内的神经干细胞(NSC)利基。O2紧张更低,低氧诱导因子1α(HIF1alpha)促进信号转导途径,促进自我更新(例如,切口)和抑制通路,促进NSC分化或凋亡(如骨形态形成的蛋白质)。降解HIF1alpha,从而促进国家安全委员会和分化或凋亡祖细胞。可以模拟优化体外生产方法细胞替代疗法。相反,O2的可用性会中断在疾病,如中风或关键的作用大脑肿瘤恶化。激活前体体内增殖,而恶性胶质瘤干细胞增殖最大限度比正常的干细胞更缺氧的环境细胞,这可能使他们对某些anti-neoplastic疗法。O2反应是正常的核心体系结构和安全委员会监管和动态在脑部疾病的病因和治疗。

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