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  - 2015 Jan 01
TA  - bioRxiv
PG  - 007831
4099  - http://biorxiv.org/content/early/2015/01/30/007831.short
4100  - http://biorxiv.org/content/early/2015/01/30/007831.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. However, existing mathematical models with few state variables and fixed parameters are inadequate in characterizing the temporal transformation of the landscape. Here we simulate a decision-switch model of gene regulation with more than two state variables and with time-varying repression among regulatory factors. We are able to demonstrate multi-lineage differentiation at different timescales that portrays the branching canals in Waddington’s illustration. We also present a repressilator-type system that activates suppressed genes via sustained oscillations in a flattened landscape, hence providing an alternative scheme for cellular reprogramming. The time-dependent parameters governed by gradient-based dynamics regulate cell differentiation, dedifferentiation and transdifferentiation. Our prediction integrates the theories of branching and structural oscillations in cell-fate determination, which reveals key temporal patterns of cell differentiation and associated diseases, such as cancer.