TY - JOUR T1 - Self-Organizing Global Gene Expression Regulated Through Criticality: The Mechanism of Cell Fate Change JF - bioRxiv DO - 10.1101/066498 SP - 066498 AU - Masa Tsuchiya AU - Alessandro Giuliani AU - Midori Hashimoto AU - Jekaterina Erenpreisa AU - Kenichi Yoshikawa Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/07/28/066498.abstract N2 - Background A fundamental issue in bioscience is to understand the underlying mechanism of the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome regulating cell fate change. We address this issue by elucidating a physically motivated self-organizing mechanism.Principal Findings 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 population and single cell levels. The novel findings are: Mechanism of cell fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). Cell fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of an initial-state critical behaviors (criticality). Most notably, reprograming of the 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.Perturbation mechanism of SOC controls: Global perturbations of the SOC controls involve the temporal regulation of critical states. Elucidation of the dynamic interaction of critical states in terminal cell fates reveals that sub-critical states (ensembles of genes for which expression undergoes only very limited changes during the process) act as a ‘source’ to sustain global perturbations, whereas super-critical states (ensembles of genes for which expression varies greatly) behave as a ‘sink’ to form a dominant cyclic state-flux with sub-critical states through the cell nuclear environment.Conclusion and Significance The ‘whole-genome’ level of gene expression regulation, where the collective behavior of low-variance genes plays a central role in genome-wide self-organization, complements the microscopic gene-by-gene fine tuning, and represents a still largely unexplored thermodynamically regulated mechanism responsible for massive genome expression reprogramming. ER -