Modeling relaxation experiments with a mechanistic model of gene expression

Abstract

AbstractBackgroundIn the present work, we aimed at modeling a relaxation experiment which consists in selecting a subfraction of a cell population and observing the speed at which the entire initial distribution for a given marker is reconstituted.MethodsFor this we first proposed a modification of a previously published mechanistic two-state model of gene expression to which we added a state-dependent proliferation term. This results in a system of two partial differential equations. Under the assumption of a linear proliferation rate, we could derive the asymptotic profile of the solutions of this model.ResultsIn order to confront our model with experimental data, we generated a relaxation experiment of the CD34 antigen on the surface of TF1-BA cells, starting either from the highest or the lowest CD34 expression levels. We observed in both cases that after approximately 25 days the distribution of CD34 returns to its initial stationary state. Numerical simulations, based on parameter values estimated from the dataset, have shown that the model solutions closely align with the experimental data from the relaxation experiments.ConclusionAltogether our results strongly support the notion that cells should be seen and modeled as probabilistic dynamical systems.