Investigating the Role of Network Topology and Dynamical Regimes on the Dynamics of a Cell Differentiation Model

The characterization of the generic properties underlying the complex interplay ruling cell differentiation is one of the goals of modern biology. To this end, we rely on a powerful and general dynamical model of cell differentiation, which defines differentiation hierarchies on the basis of the stability of gene activation patterns against biological noise. In particular, in this work we investigate the role of the topology (i.e. scale-free or random) and of the dynamical regime (i.e. ordered, critical or disordered) of gene regulatory networks on the model dynamics. Two real lineage commitment trees, i.e. intestinal crypts and hematopoietic cells, are compared with the hierarchies emerging from the dynamics of ensembles of randomly simulated networks. Briefly, critical networks with random topology seem to display a wider range of possible behaviours as compared to the others, hence suggesting an intrinsic dynamical heterogeneity that may be fundamental in defining different differentiation trees. Conversely, scale-free networks show a generally more ordered dynamics, which limit the overall variability, yet containing the effect of possible genomic perturbations. Interestingly, a considerable number of networks across all types show emergent trees that are biologically plausible, suggesting that a relatively wide portion of the networks space may be suitable, without the need for a fine tuning of the parameter