The role of oxygen availability in embryonic development and stem cell function

Low levels of oxygen (O-2) occur naturally in developing embryos. Cells respond to their hypoxic microenvironment by stimulating several hypoxia-inducible factors (and other molecules that mediate O-2 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 O-2 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.