Dynamical-systems theory of cellular reprogramming

TL;DR

This paper models cellular reprogramming as a dynamical system, showing how gene expression oscillations and epigenetic changes drive cells toward pluripotency through a universal attractor mechanism.

Contribution

It introduces a dynamical-systems framework for understanding cellular reprogramming, highlighting the role of oscillatory gene expression and epigenetic interactions as a universal attraction to pluripotency.

Findings

Repressilator model confirms the attraction to pluripotency.

Random gene networks exhibit similar reprogramming dynamics.

Embryonic stem cell networks align with the proposed dynamical scheme.

Abstract

In cellular reprogramming, almost all epigenetic memories of differentiated cells are erased by the overexpression of few genes, regaining pluripotency, potentiality for differentiation. Considering the interplay between oscillatory gene expression and slower epigenetic modifications, such reprogramming is perceived as an unintuitive, global attraction to the unstable manifold of a saddle, which represents pluripotency. The universality of this scheme is confirmed by the repressilator model, and by gene regulatory networks randomly generated and those extracted from embryonic stem cells.