A Model for Genetic and Epigenetic Regulatory Networks Identifies Rare Pathways for Transcription Factor Induced Pluripotency
Figure 5
Reprogramming is a consequence of random perturbation of epigenetic state of the cell.
In our model, reprogramming factors can change the epigenetic state of randomly chosen regulatory modules (for reasons, see text). (a) Starting from a fully differentiated state, reprogramming factors can perturb any of the remaining 14 positions (for the case of a 4-level hierarchy). Four outcomes are possible depending on the perturbation site: death/arrest, trans-differentiation, de-differentiation or return to the initial cellular state. These outcomes are determined by simulating the system in accord with the rules described in the text and Figs. 2–3. The color code representing genetic and epigenetic states is the same as in Fig. 1 (b) Examples of real trajectories observed in simulations illustrating different temporal evolution of epigenetic and genetic states. Complete cell reprogramming appears as a consequence of several successful de-differentiation events as seen in the second example trajectory. Simulations are performed with parameter values F = 2000; J = 3000; G = 25; H = 40; a = 0; b = 0.3. The color code representing genetic and epigenetic states is the same as in Fig. 1.