Single-cell reprogramming in mouse embryo development through a critical transition state

Masa Tsuchiya, Alessandro Giuliani, Kenichi Yoshikawa

Research output: Contribution to journalArticlepeer-review


Our previous work on the temporal development of the genome-expression profile in single-cell early mouse embryo indicated that reprogramming occurs via a critical transition state, where the critical-regulation pattern of the zygote state disappears. In this report, we unveil the detailed mechanism of how the dynamic interaction of thermodynamic states (critical states) enables the genome system to pass through the critical transition state to achieve genome reprogramming right after the late 2-cell state. Self-organized criticality (SOC) control of overall expression provides a snapshot of self-organization and explains the coexistence of critical states at a certain experimental time point. The time-development of self-organization is dynamically modulated by changes in expression flux between critical states through the cell nucleus milieu, where sequential global perturbations involving activation-inhibition of multiple critical states occur from the middle 2-cell to the 4-cell state. Two cyclic fluxes act as feedback flow and generate critical-state coherent oscillatory dynamics. Dynamic perturbation of these cyclic flows due to vivid activation of the ensemble of low-variance expression (sub-critical state) genes allows the genome system to overcome a transition state during reprogramming. Our findings imply that a universal mechanism of long-term global RNA oscillation underlies autonomous SOC control, and the critical gene ensemble at a critical point (CP) drives genome reprogramming. Identification of the corresponding molecular players will be essential for understanding single-cell reprogramming.

Original languageEnglish
Article number584
Issue number11
Publication statusPublished - Nov 1 2017


  • Critical gene ensemble
  • Critical states
  • Non-equilibrium dynamics
  • Self-organized criticality
  • Single-cell early embryo development
  • Single-cell reprogramming
  • Statistical thermodynamics
  • Transition state

ASJC Scopus subject areas

  • Physics and Astronomy(all)


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