Abstract
GATA1-PU.1 genetic switch is a paradigmatic genetic switch that governs the differentiation of progenitor cells into two different fates, erythroid and myeloid fates. In terms of dynamical model representation of these fates or lineages corresponds to stable attractor and choosing between the attractors. Small asymmetries and stochasticity intrinsically present in all genetic switches lead to the effect of delayed bifurcation which will change the differentiation result according to the timing of the process and affect the proportion of erythroid versus myeloid cells. We consider the differentiation bifurcation scenario in which there is a symmetry-breaking in the bifurcation diagrams as a result of asymmetry in external signaling. We show that the decision between two alternative cell fates in this structurally symmetric decision circuit can be biased depending on the speed at which the system is forced to go through the decision point. The parameter sweeping speed can also reduce the effect of asymmetry and produce symmetric choice between attractors, or convert the favorable attractor. This conversion may have important contributions to the immune system when the bias is in favor of the attractor which gives rise to non-immune cells.
Highlights
The importance of studying the immune system has attracted mathematicians and biologists to discover more of its features in recent years
An important question arises in these models about the causes of bifurcation and symmetry-breaking and whether they occur in response to intrinsic cues or extrinsic signals
A question naturally arises how rate dependent signaling will affect the immune cell-fate selection via a differentiation of progenitor cells. We have studied these phenomena in the most paradigmatic switch responsible for the differentiation of immune cells, the GATA1-PU.[1] switch
Summary
The importance of studying the immune system has attracted mathematicians and biologists to discover more of its features in recent years. The integration of both intrinsic and extrinsic factors has received an extensive attention to elucidate the roles of external signals in cell-fate decision processes, and most importantly its relationship to the production of immune cells (3–6). Another important and interesting factor that can affect the decision of the cell is the speed of external signals or the speed of crossing the critical region (7–9). A question naturally arises how rate dependent signaling will affect the immune cell-fate selection via a differentiation of progenitor cells We have studied these phenomena in the most paradigmatic switch responsible for the differentiation of immune cells, the GATA1-PU.[1] switch. We will test the effect of parameter sweeping speed on the distribution of trajectories in the attractors of the dynamical system
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