The cardiac hypoxic niche: emerging role of hypoxic microenvironment in cardiac progenitors

Resident stem cells persist throughout the entire lifetime of an organism where they replenishing damaged cells. Numerous types of resident stem cells are housed in a low-oxygen tension (hypoxic) microenvironment, or niches, which seem to be critical for survival and maintenance of stem cells. Recently our group has identified the adult mammalian epicardium and subepicardium as a hypoxic niche for cardiac progenitor cells. Similar to hematopoietic stem cells (LT-HSCs), progenitor cells in the hypoxic epicardial niche utilize cytoplasmic glycolysis instead of mitochondrial oxidative phosphorylation, where hypoxia inducible factor 1 alpha (Hif-1 alpha) maintains them in glycolytic undifferentiated state. In this review we summarize the relationship between hypoxic signaling and stem cell function, and discuss potential roles of several cardiac stem/progenitor cells in cardiac homeostasis and regeneration.