Oscillatory Dynamics of Heterogeneous Stem Cell Regeneration

Abstract

Stem cell regeneration is an essential biological process in the maintenance of tissue homeostasis; dysregulation of stem cell regeneration may result in dynamic diseases that show oscillations in cell numbers. Cell heterogeneity and plasticity are necessary for the dynamic equilibrium of tissue homeostasis; however, how these features may affect the oscillatory dynamics of the stem cell regeneration process remains poorly understood. Here, based on a mathematical model of heterogeneous stem cell regeneration that includes cell heterogeneity and random transition of epigenetic states, we study the conditions to have oscillation solutions through bifurcation analysis and numerical simulations. Our results show various model system dynamics with changes in different parameters associated with kinetic rates, cellular heterogeneity, and plasticity. We show that introducing heterogeneity and plasticity to cells can result in oscillation dynamics, as we have seen in the homogeneous stem cell regeneration system. However, increasing the cell heterogeneity and plasticity intends to maintain tissue homeostasis under certain conditions. The current study is an initiatory investigation of how cell heterogeneity and plasticity may affect stem cell regeneration dynamics, and many questions remain to be further studied both biologically and mathematically.