From Cell States to Cell Fates: Control of Cell State Transitions

Abstract

We examine the coordinated behavior of thousands of genes in cell fate transitions through genome expression as an integrated dynamical system using the concepts of self-organized criticality and coherent stochastic behavior. To quantify the effects of the collective behavior of genes, we adopted the flux balance approach and developed it in a new tool termed expression flux analysis (EFA). Here we describe this tool and demonstrate how its application to specific experimental genome-wide expression data provides new insights into the dynamics of the cell-fate transitions. Particularly, we show that in cell fate change, specific stochastic perturbations can spread over the entire system to guide distinct cell fate transitions through switching cyclic flux flow in the genome engine. Utilization of EFA enables us to elucidate a unified genomic mechanism for when and how cell-fate change occurs through critical transitions.

Keywords: Biological regulation; Cell fate; Critical point; Flux analysis; Genome attractor; Genome engine; Genome expression; Nonequilibrium thermodynamics; Open systems; Self-organized criticality (SOC); Transition theory.