Cell fate determination, the process through which cells commit to differentiated states , has been shown to be mediated by gene regulatory motifs with mutually exclusive expression states. The classical picture for deterministic cell decision making includes bistability and hysteresis . Despite numerous experimental works supporting evidence of hysteresis in gene regulatory networks , such phenomenon may not be compatible with the stochasticityunderlying gene regulation dynamics. Here we show how under sufficiently slow dynamics, the dependency of the transient solutions on the initial state of the cells can be mistakenly interpreted as hysteresis and, to quantify this phenomenon, we provide an estimate of the convergence rate to the equilibrium. We also introduce the equation of a natural landscape capturing the evolution of the system that, unlike traditional cell fate potential landscapes, is compatible with the notion of coexistence at the microscopic level.
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, the 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. In this work, we provide a quantitative description of a transient hysteresis phenomenon that reconciles experimental evidence of hysteretic behaviour in gene regulatory networks with their inherent stochasticity. Under sufficiently slow dynamics, the dependency of the non-stationary solutions on the initial state of the cells can lead to what we denote here as transient hysteresis. To quantify this phenomenon, we provide an estimate of the convergence rate to the equilibrium. We also introduce the equation of a natural landscape capturing the evolution of the system that, unlike traditional cell fate potential landscapes, is compatible with the notion of coexistence at the microscopic level.
R
, has been shown to be
is commonly
R
picture for deterministic cell decision making
deterministic picture for cell fate determination
R
. Despite numerous experimental works supporting evidence of hysteresis
, which enables the persistence of the acquired cellular state after withdrawal of the stimulus, ensuring a robust cellular response. However, the 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. In this work, we provide a quantitative description of a transient hysteresis phenomenon that reconciles experimental evidence of hysteretic behaviour
R
, such phenomenon may not be compatible with the stochasticityunderlying gene regulation dynamics. Here we show how under
with their inherent stochasticity. Under
R
transient
non-stationary
R
be mistakenly interpreted as hysteresis and, to
lead to what we denote here as transient hysteresis. To