Abstract
Molecular oxygen has been known to play a critical role in a wide range of biological processes including glycolysis, mitochondrial respiration, angiogenesis, pulmonary functions, and cardiovascular activities. An emerging theme has developed in recent years that oxygen has significant impact on embryonic development, maintenance of stem cells, and cellular differentiation or cell fate decisions. Among the notable observations, early embryonic development takes place in a hypoxic microenvironment. Hematopoietic stem cells appear to be located in hypoxic regions within the bone marrow. Majority of the current observations have shown that hypoxia seems to prevent cellular differentiation and to maintain pluripotency of stem/progenitor cells. Genetic studies have demonstrated a critical role of hypoxia-inducible factors 1alpha and 2alpha in embryonic development. These intriguing observations demonstrate an important role of molecular oxygen in such fundamental biological processes as stem cell maintenance and regulation of cell fate decisions. Herein, we describe some of the latest advances in the biology of molecular oxygen and provide our perspectives on the potential impact of these interesting findings.
Highlights
Molecular oxygen (O2) is an essential element for life on earth
We have found that hypoxia increases the expression of the stem/progenitor marker pref-1/DLK1 (Lin et al 2006), a negative regulator of adipogenic differentiation (Smas and Sul, 1993; Wang et al 2006)
The last 500 million years have witnessed a dramatic fluctuation in atmospheric O2 between 35% and 15% (Berner et al 2007; Massabuau, 2003)
Summary
Molecular oxygen (O2) is an essential element for life on earth. It is the ultimate electron acceptor in the mitochondrial electron transport chain and is the only cellular nutrient in a gaseous form. While others used ex vivo human placental tissues, Maltepe et al used an in vitro model of trophoblast stem cells initially derived from mouse embryonic fibroblasts. Consistent with these observations, expression of HIF-2α mRNA increases with adipogenic differentiation and HIF-2α protein is regulated by O2-independent mechanisms in adipocytes (Lin et al 2006).
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