A computational scheme connecting gene regulatory network dynamics with heterogeneous stem cell regeneration

Abstract: Stem cell regeneration is a vital biological process in self-renewing tissues, governing development and tissue homeostasis. Gene regulatory network dynamics are pivotal in controlling stem cell regeneration and cell type transitions. However, integrating the quantitative dynamics of gene regulatory networks at the single-cell level with stem cell regeneration at the population level poses significant challenges. This study presents a computational framework connecting gene regulatory network dynamics with stem cell regeneration through a data-driven formulation of the inheritance function. The inheritance function captures epigenetic state transitions during cell division in heterogeneous stem cell populations. Our scheme allows the derivation of the inheritance function based on a hybrid model of cross-cell-cycle gene regulation network dynamics. The proposed scheme enables us to derive the inheritance function based on the hybrid model of cross-cell-cycle gene regulation network dynamics. By explicitly incorporating gene regulatory network structure, it replicates cross-cell-cycling gene regulation dynamics through individual-cell-based modeling. The numerical scheme holds the potential for extension to diverse gene regulatory networks, facilitating a deeper understanding of the connection between gene regulation dynamics and stem cell regeneration.