Physical Review Research (Apr 2022)
Dynamical systems theory of cellular reprogramming
Abstract
In cellular reprogramming, almost all epigenetic memories of differentiated cells are erased by the overexpression of a few genes, resulting in regaining pluripotency, the potential 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 that are randomly generated and extracted from embryonic stem cells.