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Gene expression dynamics in the macrophage exhibit criticality.

ABSTRACT: Cells are dynamical systems of biomolecular interactions that process information from their environment to mount diverse yet specific responses. A key property of many self-organized systems is that of criticality: a state of a system in which, on average, perturbations are neither dampened nor amplified, but are propagated over long temporal or spatial scales. Criticality enables the coordination of complex macroscopic behaviors that strike an optimal balance between stability and adaptability. It has long been hypothesized that biological systems are critical. Here, we address this hypothesis experimentally for system-wide gene expression dynamics in the macrophage. To this end, we have developed a method, based on algorithmic information theory, to assess macrophage criticality, and we have validated the method on networks with known properties. Using global gene expression data from macrophages stimulated with a variety of Toll-like receptor agonists, we found that macrophage dynamics are indeed critical, providing the most compelling evidence to date for this general principle of dynamics in biological systems.

SUBMITTER: Nykter M

PROVIDER: S-EPMC2538855 | biostudies-other | 2008 Feb

REPOSITORIES: biostudies-other

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Gene expression dynamics in the macrophage exhibit criticality.

Nykter Matti M Price Nathan D ND Aldana Maximino M Ramsey Stephen A SA Kauffman Stuart A SA Hood Leroy E LE Yli-Harja Olli O Shmulevich Ilya I

Proceedings of the National Academy of Sciences of the United States of America 20080204 6

Cells are dynamical systems of biomolecular interactions that process information from their environment to mount diverse yet specific responses. A key property of many self-organized systems is that of criticality: a state of a system in which, on average, perturbations are neither dampened nor amplified, but are propagated over long temporal or spatial scales. Criticality enables the coordination of complex macroscopic behaviors that strike an optimal balance between stability and adaptability ...[more]

PMID: 18250330

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Project description:BackgroundThe underlying mechanism of dynamic control of the genome-wide expression is a fundamental issue in bioscience. We addressed it in terms of phase transition by a systemic approach based on both density analysis and characteristics of temporal fluctuation for the time-course mRNA expression in differentiating MCF-7 breast cancer cells.MethodologyIn a recent work, we suggested criticality as an essential aspect of dynamic control of genome-wide gene expression. Criticality was evident by a unimodal-bimodal transition through flattened unimodal expression profile. The flatness on the transition suggests the existence of a critical transition at which up- and down-regulated expression is balanced. Mean field (averaging) behavior of mRNAs based on the temporal expression changes reveals a sandpile type of transition in the flattened profile. Furthermore, around the transition, a self-similar unimodal-bimodal transition of the whole expression occurs in the density profile of an ensemble of mRNA expression. These singular and scaling behaviors identify the transition as the expression phase transition driven by self-organized criticality (SOC).Principal findingsEmergent properties of SOC through a mean field approach are revealed: i) SOC, as a form of genomic phase transition, consolidates distinct critical states of expression, ii) Coupling of coherent stochastic oscillations between critical states on different time-scales gives rise to SOC, and iii) Specific gene clusters (barcode genes) ranging in size from kbp to Mbp reveal similar SOC to genome-wide mRNA expression and ON-OFF synchronization to critical states. This suggests that the cooperative gene regulation of topological genome sub-units is mediated by the coherent phase transitions of megadomain-scaled conformations between compact and swollen chromatin states.Conclusion and significanceIn summary, our study provides not only a systemic method to demonstrate SOC in whole-genome expression, but also introduces novel, physically grounded concepts for a breakthrough in the study of biological regulation.

Project description:Hibernation has been selected for increasing survival in harsh climatic environments. Seasonal variability in temperature may push the body temperatures of hibernating animals across boundaries of alternative states between euthermic temperature and torpor temperature, typical of either hibernation or summer dormancy. Nowadays, wearable electronics present a promising avenue to assess the occurrence of criticality in physiological systems, such as body temperature fluctuating between attractors of activity and hibernation. For this purpose, we deployed temperature loggers on two hibernating edible dormice for an entire year and under Mediterranean climate conditions. Highly stochastic body temperatures with sudden switches over time allowed us to assess the reliability of statistical leading indicators to anticipate tipping points when approaching a critical transition. Hibernation dynamics showed flickering, a phenomenon occurring when a system rapidly moves back and forth between two alternative attractors preceding the upcoming major regime shift. Flickering of body temperature increased when the system approached bifurcations, which were also anticipated by several metric- and model-based statistical indicators. Nevertheless, some indicators did not show a pattern in their response, which suggests that their performance varies with the dynamics of the biological system studied. Gradual changes in air temperature drove transient between states of hibernation and activity, and also drove hysteresis. For hibernating animals, hysteresis may increase resilience when ending hibernation earlier than the optimal time, which may occur in regions where temperatures are sharply rising, especially during winter. Temporal changes in early indicators of critical transitions in hibernation dynamics may help to understand the effects of climate on evolutionary life histories and the plasticity of hibernating organisms to cope with shortened hibernation due to global warming.

Project description:BackgroundA 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.Principal findingsBuilding 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.Conclusion and significance'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.

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Gene expression dynamics in the macrophage exhibit criticality.

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Gene expression dynamics in the macrophage exhibit criticality.

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