Fig. 4

The Nanog expression level during induction with different strategies of iPS cell reprogramming. a, c, e Three reprogramming strategies of activating Oct4 and Sox2. a mild induction (C₀ = C _S  = 0.1): the high-Nanog subpopulation still makes up the majority; (c) strong induction (C₀ = C _S  = 0.3): the low-Nanog subpopulation becomes the majority and reduces the reprogramming efficiency; (e) strong induction with additional Nanog activation (C₀ = C _S  = C _N  = 0.3): the low-Nanog subpopulation disappears and only high-Nanog state remains. The green curves are the ODE trajectories of induced cell reprogramming path started from the ME differentiated state. The backgrounds are the potential landscapes after induction, showing the equilibrium distribution of high-Nanog / low-Nanog subpopulations when external inductions are turned on. b, d, f The equilibrium distribution of Oct4 and Nanog among simulated cell population (N = 10,000) after induction: (b) the fraction of low-Nanog subpopulation for mild induction is 47.3%; (d) the fraction of low-Nanog subpopulation for strong induction is up to 97.9%; (f) almost no low-Nanog subpopulation for strong induction of Oct4 and Sox2 coupled with additional Nanog activation