@article {Rabajante007831, author = {Jomar Fajardo Rabajante and Ariel Lagdameo Babierra}, title = {Branching and oscillations in the epigenetic landscape of cell-fate determination}, elocation-id = {007831}, year = {2014}, doi = {10.1101/007831}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The well-known Waddington{\textquoteright}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{\textquoteright}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{\textquoteright}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.}, URL = {https://www.biorxiv.org/content/early/2014/09/04/007831}, eprint = {https://www.biorxiv.org/content/early/2014/09/04/007831.full.pdf}, journal = {bioRxiv} }