Role of mild hypoxia in cell development

在我们对中枢神经系统(CNS)发育的理解上有几个明显的差距。人们普遍认为，在未成熟和成熟的哺乳动物中，神经前体细胞库(NPC；一种更成熟的干细胞)可以发育和成熟为不同类型的神经系统细胞(如神经元和支持细胞)。然而，介导这些变化所需的细胞信号以及环境氧对这种成熟过程的影响还没有得到充分的研究。研究表明，在发育中的中枢神经系统中，各种释放的因子启动了鼻咽癌的成熟和从遥远的来源迁移。关于这些因素的来源，除了它们是如何释放的(总是释放或刺激释放)，人们知之甚少。这些研究的第二个目的是调查不同的氧气环境在鼻咽癌发展中的作用。干细胞生物学的研究通常使用大气中的氧气(21%氧气)或缺氧(0%氧气)来研究前体细胞的发育。与这些细胞或组织正常暴露的环境相比，大气中的氧气是高氧(高氧气水平)。例如，在发育中的胎儿，动脉血氧水平在(5-8%氧气)的范围内。尽管成年哺乳动物的动脉血氧水平较高，但仍低于大多数研究中使用的水平。氧可能通过激活蛋白质信号通路或激活控制细胞兴奋性的膜离子通道以及钙和其他离子的内流来调节细胞的行为。由于这些蛋白质和离子通道的激活通常发生在特定浓度的氧上，因此了解生理上相关的氧水平对神经前体细胞发育的影响是很重要的。这将有助于我们更好地了解中枢神经系统的发育，以及成熟神经系统中发生的重塑途径。

There are several significant gaps in our understanding of central nervous system (CNS) development. It is widely understood that pools of neural precursor cells (NPC; a more mature stem cell) can develop and mature into different cell types of the nervous system (e.g. neurons and supportive cells) in both the immature and mature mammal. However the cellular signaling required to mediate these changes and the effect of environmental oxygen has on this maturation process have not been fully investigated. Studies suggest that various released factors, in the developing CNS, initiate the maturation and migration of NPC from distant sources. Little is known as to the source of these factors, in addition to how they are released (always released or stimulated release). The second aim of these studies is to investigate the role of different oxygen environments may have on NPC development. Often research in stem cell biology uses atmospheric oxygen (21% oxygen) or anoxia (<0% oxygen) in the study of precursor cell development. In comparison to the environment that these cells or tissue are normally exposed to, atmospheric oxygen is hyperoxic (high oxygen levels). For example in the developing fetus, arterial oxygen levels are in the range of (5-8% oxygen). Although arterial oxygen levels are higher in the mature mammal, it is still lower than that used in most studies. Oxygen may modulate cellular behavior via activation of protein signaling pathways or activation of membrane ion channels that control cellular excitability and the influx of calcium and other ions. Since activation of these proteins and ion channels typically occurs over specific concentrations of oxygen, it is important to understand the effects of physiologically relevant oxygen levels have on neural precursor cell development. This will help improve our understanding of CNS development in addition to the remodeling pathways that occur in the mature nervous system.