title: Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change.
abstract: BACKGROUND
  A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization.
  
  
  RESULTS
  Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change.
  
  
  CONCLUSIONS
  'Whole-genome' regulation of gene expression through self-regulatory SOC control complements gene-by-gene fine tuning and represents a still largely unexplored non-equilibrium statistical mechanism that is responsible for the massive reprogramming of genome expression.
authors.affiliation: Systems Biology Program, School of Media and Governance, Keio University, Fujisawa, Japan.
authors.forename: Masa
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Environment and Health Department, Istituto Superiore di Sanitá, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
authors.affiliation: Graduate School of Frontier Science, the University of Tokyo, Kashiwa, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Latvian Biomedical Research & Study Centre, Riga, Latvia.
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Erenpreisa
authors.affiliation: Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D008954:Models, Biological