Transient hysteresis and inherent stochasticity in gene regulatory networks

• Published in: Nature communications Vol. 10; no. 1; pp. 4581 - 7
• Main Authors: Pájaro, M, Otero-Muras, I, Vázquez, C, Alonso, A A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.10.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Bistability; Cell differentiation; Cell Differentiation - genetics; Cell fate; Computer Simulation; Gene expression; Gene Regulatory Networks; Hysteresis; Initial conditions; Landscape; Models, Genetic; Organic chemistry; Stochastic Processes; Stochasticity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12344-w

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.