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Speed-dependent cellular decision making in nonequilibrium genetic circuits.

Nené, NR; Garca-Ojalvo, J; Zaikin, A; (2012) Speed-dependent cellular decision making in nonequilibrium genetic circuits. PLoS One , 7 (3) , Article e32779. 10.1371/journal.pone.0032779. Green open access

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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.

Type: Article
Title: Speed-dependent cellular decision making in nonequilibrium genetic circuits.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0032779
Publisher version: http://dx.doi.org/10.1371/journal.pone.0032779
Language: English
Additional information: © 2012 Nené et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3302799 NRN acknowledges financial support from the EPSRC at CoMPLEX, UCL, JGO from the Ministerio de Ciencia e Innovacion (Spain, project FIS2009-13360), the Spanish Multiple Sclerosis Network (REEM-ISCIII), and the ICREA Academia programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: Cell Differentiation, Computer Simulation, Gene Regulatory Networks, Models, Biological, Signal Transduction, Time Factors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/1353515
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