Table 3.

Experimental findings from literature compared to simulation results.

Experimental finding	Theoretical validation by our model
Somatic cells can be reprogrammed to iPSCs upon viral delivery of pluripotency factors with a very low efficiency (Takahashi, 2006)	Reprogramming experiment of our main model (Figure 2B)
iPSCs can be re-differentiated into various kinds of tissues (all three germ layers; Takahashi, 2006)	Differentiation experiment of our main model (Figure 2A)
ESCs have more euchromatin and accumulate high condensed heterochromatin as differentiation progresses (Francastel et al., 2000)	In the differentiation of the pluripotent state, which still consists of a distribution across several different chromatin and methylation configurations, we can observe a transition to more sharply defined states, which mostly include heterochromatin and methylation compositions (Figure 2A)
DNA methylation is essential for chromatin structure during development (Hashimshony et al., 2003)	In models lacking DNA methylation, differentiation as well as reprogramming are abolished and cells will not be able to pass to other states in the state space (Section 3.6.5)
Treatment of partially differentiated ES cells with the DNA demethylating agent 5-azacytidine (5-AzaC) induces de-differentiation (Tsuji-Takayama et al., 2004)	When starting from partly differentiated states in models with spontaneous demethylation mimicking 5-AzaC treatment, we observe de-differentiation and even efficient reprogramming (Section 3.6.3)
Knockdown of DnmtI reactivates retroviral genes (Wernig et al., 2007)	In models mimicking DnmtI knockdown (e.g., spontaneous demethylation in Section 3.6.3 or no methylation in Section 3.6.5 simulation from the iPS state leads to partial reactivation of retroviral genes
Dnmt3a and Dnmt3b are not required for retroviral silencing in the first 10 days of reprogramming (Pannell et al., 2000; Hotta and Ellis, 2008)	In models without dnmt activity we can still observe silencing of retroviral genes (results not explicitly shown)
The histone deacetylase (HDAC) inhibitor valproic acid is capable of enhancing reprogramming efficiency (Huangfu et al., 2008)	In models where the probability for heterochromatin formation is downregulated (mimicking inhibition of HDAC) we observe a slight increase in the reprogramming efficiency (Figure 8)