Rare-event sampling of epigenetic landscapes and phenotype transitions
Fig 6
Simulation results for the pluripotency network (Parameter Set II).
Changing DNA-Binding Kinetics Alters the Epigenetic Landscape. A) Computed eigenvalue spectrum and global timescales. B) The coarse-grained Markov State Model showing five phenotypes corresponding to the LN1, SC, PPE, TE, and IM phenotypes of Parameter Set I. The majority of the steady state probability is in the IM phenotype (0.98). C) The gene expression levels for each phenotype and their respective steady-state probabilities. D) The four most probable differentiation pathways between SC and TE phenotypes. E)The dominant pathways of (de)differentiation projected onto the GATA6, CDX2, and NANOG coordinates. The change in DNA-binding kinetics shows different transition dynamics from Parameter Set I. Here, the forward and reverse paths are the same.