Role of nitric oxide in the maintenance of pluripotency and regulation of the hypoxia response in stem cells

Figure 1 The dual roles of nitric oxide in stem cell pluripotency and apoptosis. Low amounts of nitric oxide (NO) induce the expression of Nanog, Oct4 and Sox2. This confers protection from apoptosis by down-regulating pro-apoptotic genes including Casp7, Casp9, as well as up-regulating the anti-apoptotic genes Bcl-2 and Birc6. High NO concentrations promote apoptosis markers, such as Poly (ADP-ribose) polymerase degradation, cleaved caspase-3, and increased p53 protein levels. Cells expressing Hsp70, a cyto-protective gene, are resistant to oxidative stress and enter into a differentiation program. Differentiation events are initiated by the down-regulation of Nanog and Oct4 and the expression of definitive endoderm markers, such as Pdx1 and Gata4.