Transient hysteresis and inherent stochasticity in gene regulatory networks

7 pages, 5 figures.-- This article is licensed under a Creative Commons Attribution 4.0 International License
Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes bistability and hysteresis, which enables the persistence of the acquired cellular state after withdrawal of the stimulus, ensuring a robust cellular response. However, stochasticity inherent to gene expression dynamics is not compatible with hysteresis, since the stationary solution of the governing Chemical Master Equation does not depend on the initial conditions. We provide a quantitative description of a transient hysteresis phenomenon reconciling experimental evidence of hysteretic behaviour in gene regulatory networks with inherent stochasticity: under sufficiently slow dynamics hysteresis is transient. We quantify this with an estimate of the convergence rate to the equilibrium and introduce a natural landscape capturing system’s evolution that, unlike traditional cell fate potential landscapes, is compatible with coexistence at the microscopic level
M.P. and A.A.A. acknowledge funding from grant PIE201870E041; I.O.M. acknowledges funding from Spanish MINECO (and the European Regional Development Fund) project SYNBIOCONTROL (grant number DPI2017-82896-C2-2-R). C.V. has been partially funded by the spanish MINECO project MTM2016-76497-R and Xunta de Galicia grant ED431C2018/033