Simon M Celeste, Keith Brian
Howard Hughes Medical Institute, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Nat Rev Mol Cell Biol. 2008 Apr;9(4):285-96. doi: 10.1038/nrm2354. Epub 2008 Feb 20.
Low levels of oxygen (O2) occur naturally in developing embryos. Cells respond to their hypoxic microenvironment by stimulating several hypoxia-inducible factors (and other molecules that mediate O2 homeostasis), which then coordinate the development of the blood, vasculature, placenta, nervous system and other organs. Furthermore, embryonic stem and progenitor cells frequently occupy hypoxic 'niches' and low O2 regulates their differentiation. Recent work has revealed an important link between factors that are involved in regulating stem and progenitor cell behaviour and hypoxia-inducible factors, which provides a molecular framework for the hypoxic control of differentiation and cell fate. These findings have important implications for the development of therapies for tissue regeneration and disease.
低氧水平在发育中的胚胎中自然存在。细胞通过刺激几种缺氧诱导因子(以及其他介导氧气稳态的分子)来响应其低氧微环境,这些因子随后协调血液、脉管系统、胎盘、神经系统和其他器官的发育。此外,胚胎干细胞和祖细胞经常占据低氧“龛位”,低氧调节它们的分化。最近的研究揭示了参与调节干细胞和祖细胞行为的因子与缺氧诱导因子之间的重要联系,这为低氧对分化和细胞命运的控制提供了分子框架。这些发现对组织再生和疾病治疗的发展具有重要意义。