Noise-Driven Differentiation via Gene Frustration and Epigenetic Fixation

TL;DR

This paper proposes a mechanism where stochastic gene expression and epigenetic feedback drive robust cell differentiation, with analytic insights into differentiation timing and stability.

Contribution

It introduces a novel model combining gene frustration and epigenetic fixation to explain noise-driven differentiation and its robustness.

Findings

Derived an analytic expression for differentiation time dependence on noise.

Demonstrated the concept of homeorhesis in the epigenetic landscape.

Showed regulatory interactions amplify noise to promote differentiation.

Abstract

Gene expression in cells is stochastic, yet differentiation is robust. We propose a mechanism in which frustrated genes with weakly stable intermediate expression undergo noise-driven switching between basins of attraction, followed by irreversible fate fixation through slow epigenetic feedback. Regulatory interactions amplify effective noise and promote differentiation. We derive analytic expression for the logarithmic dependence of differentiation time on noise strength and input-dependent cell-fate selection, and demonstrate homeorhesis, the dynamical robustness of the epigenetic landscape.