title: Speed-dependent cellular decision making in nonequilibrium genetic circuits.
abstract: Despite being governed by the principles of nonequilibrium transitions, gene expression dynamics underlying cell fate decision is poorly understood. In particular, the effect of signaling speed on cellular decision making is still unclear. Here we show that the decision between alternative cell fates, in a structurally symmetric circuit, can be biased depending on the speed at which the system is forced to go through the decision point. The circuit consists of two mutually inhibiting and self-activating genes, forced by two external signals with identical stationary values but different transient times. Under these conditions, slow passage through the decision point leads to a consistently biased decision due to the transient signaling asymmetry, whereas fast passage reduces and eventually eliminates the switch imbalance. The effect is robust to noise and shows that dynamic bifurcations, well known in nonequilibrium physics, are important for the control of genetic circuits.
authors.affiliation: Department of Mathematics, Imperial College London, London, United Kingdom. n.nene@imperial.ac.uk
authors.forename: Nuno R
authors.initials: NR
authors.lastname: Nené
authors.forename: Jordi
authors.initials: J
authors.lastname: Garca-Ojalvo
authors.forename: Alexey
authors.initials: A
authors.lastname: Zaikin
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D003198:Computer Simulation; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013997:Time Factors