Noise-Driven Differentiation via Gene Frustration and Epigenetic Fixation

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.