Figure 5.

Model for stem cell differentiation. During ES cell differentiation, Nanog and Oct4 expression is downregulated and nascent epigenetic modifications occur. At this point, nitric oxide can participate in transient downregulation of pluripotency network and also in chromatin remodelling events. Nevertheless, Nanog can be reexpressed in transient differentiated precursors. By this, fluctuating levels of Nanog and Oct4 constitute an “opportunity” for commitment through specific lineage differentiation. Nitric oxide participates in this perturbation, but further intrinsic or environmental stimuli are needed for correct commitment decision.