Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination.

ABSTRACT: The process of cell fate determination has been depicted intuitively as cells travelling and resting on a rugged landscape, which has been probed by various theoretical studies. However, few studies have experimentally demonstrated how underlying gene regulatory networks shape the landscape and hence orchestrate cellular decision-making in the presence of both signal and noise. Here we tested different topologies and verified a synthetic gene circuit with mutual inhibition and auto-activations to be quadrastable, which enables direct study of quadruple cell fate determination on an engineered landscape. We show that cells indeed gravitate towards local minima and signal inductions dictate cell fates through modulating the shape of the multistable landscape. Experiments, guided by model pre

SUBMITTER: Wu F 

PROVIDER: S-EPMC5388541 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature