Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

TL;DR

This paper introduces biologically-inspired mathematical models that generate oscillations to explain cell differentiation, offering new dynamical scenarios as alternatives to traditional epigenetic landscape frameworks.

Contribution

The authors propose simple, generic models for cell differentiation that produce oscillations, revealing two dynamical scenarios involving control parameter variations, and analyze their bifurcations.

Findings

Models generate oscillations in cell fate processes

Two dynamical scenarios identified for differentiation

Repressilator variants exhibit characteristic bifurcations

Abstract

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington's epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.