PT - JOURNAL ARTICLE AU - Jomar Fajardo Rabajante AU - Ariel Lagdameo Babierra TI - Branching and oscillations in the epigenetic landscape of cell-fate determination AID - 10.1101/007831 DP - 2014 Jan 01 TA - bioRxiv PG - 007831 4099 - http://biorxiv.org/content/early/2014/09/04/007831.short 4100 - http://biorxiv.org/content/early/2014/09/04/007831.full AB - The well-known Waddington’s epigenetic landscape of cell-fate determination is not static but varies because of the dynamic gene regulation during development. Mathematical models of bistability cannot fully characterize the landscape’s temporal transformation because of limited number of state variables and fixed parameters. Here we simulate a model of gene regulation with more than two state variables and time-varying repression among regulatory factors. We are able to show sequential multi-lineage differentiation at different timescales that portrays the branching canals in Waddington’s illustration. We also show that a repressilator-type system activates suppressed genes by producing sustained oscillations in a flattened landscape, hence providing an alternative strategy for cellular reprogramming. The time-varying parameters governed by gradient-based dynamics dampen these oscillations resulting in dedifferentiation. The high-dimensional model integrates the theories of branching and oscillations in cell-fate determination, which further explains the mechanisms of cell differentiation and associated diseases, such as cancer.