Figure 8.

Presence of substates within the “ON” state of the core Nanog switch. Steady state protein concentrations obtained for strong autocrine feedback (a=2) as a function of the autocrine ligand decay parameter δ _FGF which is sensitive to the efficiency of autocrine ligand capture (a). The abrupt change and the hysteresis indicates the existence of distinct sub-states. Both sub-states are within the “ON” state of the core NANOG circuit as the parameters identified in Figure 4, like B _Sox2,NANOG, the the binding energy of NANOG to the Sox2 promoter, are still able to shut off Nanog expression (solid symbols). The switch between the “ON” and “OFF” states continues to involve a bifurcation as the sudden jumps and hysteresis indicates (b). The “ON” and “OFF” states as well as the two substates can be visualized in a three dimensional parameter space, where the steady state NANOG concentration is plotted as a function of the the autocrine ligand decay parameter δ _FGF, and the binding energy of NANOG at the Sox2 locus, B _Sox2,NANOG (c). Concentrations are presented in the units of nM.