Simulation recapitulates distinct PSC states Simulation recapitulates distinct PSC states Simulation inputs for LIF+Serum (LS: orange), 2i+LIF (2iL: red), and bFGF+Activin (bF+A: green) conditions.Condition‐dependent pluripotent cell populations correspond to strongly connected components (SCCs) in the state transition graphs of asynchronously updated Boolean models. Gray dots represent unique profiles, and edges represent state transitions among the profiles. Colored edges indicate the transitions within population‐specific SCCs. The number of simulations and the number of steps in each simulation were 300‐100, 300‐100, 300‐300 for LS, 2iL, and bF+A condition, respectively.Pinwheel diagram of relative population‐averaged expression levels in predicted states (shaded area) under different input conditions (red—mESC conditions, green—EpiSC conditions) recapitulates experimental gene expression data (solid lines) from microarray and RNA‐seq studies.In silico single gene GOF/LOF analysis of mESCs and EpiSCs was performed by fixing each gene in the GRN as ON or OFF, in either mESC (LS—orange) or EpiSC (bF+A—green) conditions. The calculated gene expression levels following each manipulation were mapped onto principle component analysis (PCA) metrics. The individual gene perturbations that resulted in the changing of overall gene expression of EpiSCs to a more mESC‐like one (green dots in orange shaded space) were predicted candidates for driving reversion from EpiSCs to mESCs. Ayako Yachie‐Kinoshita et al. Mol Syst Biol 2018;14:e7952 © as stated in the article, figure or figure legend