Regulative Differentiation as Bifurcation of Interacting Cell Population

TL;DR

This paper presents a dynamical systems model showing how cell-cell interactions can regulate cell differentiation and population ratios through bifurcation mechanisms, providing insights into multicellular development.

Contribution

It introduces a novel bifurcation-based mechanism for cell differentiation driven by intercellular interactions, with models that preserve cell population ratios.

Findings

Cell fate switching occurs via bifurcation in models with positive-feedback loops.

Population ratios of cell types are maintained despite changes in total cell number.

Differentiation is explained as a bifurcation phenomenon influenced by cell-cell interactions.

Abstract

In multicellular organisms, several cell states coexist. For determining each cell type, cell-cell interactions are often essential, in addition to intracellular gene expression dynamics. Based on dynamical systems theory, we propose a mechanism for cell differentiation with regulation of populations of each cell type by taking simple cell models with gene expression dynamics. By incorporating several interaction kinetics, we found that the cell models with a single intracellular positive-feedback loop exhibit a cell fate switching, with a change in the total number of cells. The number of a given cell type or the population ratio of each cell type is preserved against the change in the total number of cells, depending on the form of cell-cell interaction. The differentiation is a result of bifurcation of cell states via the intercellular interactions, while the population regulation is explained by self-consistent determination of the bifurcation parameter through cell-cell interactions. The relevance of this mechanism to development and differentiation in several multicellular systems is discussed.