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      Multi-synchronization and other patterns of multi-rhythmicity in oscillatory biological systems

      review-article
      1 , , 2 ,
      Interface Focus
      The Royal Society
      oscillations, biological rhythms, synchronization, birhythmicity, bistability, computational systems biology

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          Abstract

          While experimental and theoretical studies have established the prevalence of rhythmic behaviour at all levels of biological organization, less common is the coexistence between multiple oscillatory regimes (multi-rhythmicity), which has been predicted by a variety of models for biological oscillators. The phenomenon of multi-rhythmicity involves, most commonly, the coexistence between two (birhythmicity) or three (trirhythmicity) distinct regimes of self-sustained oscillations. Birhythmicity has been observed experimentally in a few chemical reactions and in biological examples pertaining to cardiac cell physiology, neurobiology, human voice patterns and ecology. The present study consists of two parts. We first review the mechanisms underlying multi-rhythmicity in models for biochemical and cellular oscillations in which the phenomenon was investigated over the years. In the second part, we focus on the coupling of the cell cycle and the circadian clock and show how an additional source of multi-rhythmicity arises from the bidirectional coupling of these two cellular oscillators. Upon bidirectional coupling, the two oscillatory networks generally synchronize in a unique manner characterized by a single, common period. In some conditions, however, the two oscillators may synchronize in two or three different ways characterized by distinct waveforms and periods. We refer to this type of multi-rhythmicity as ‘multi-synchronization’.

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          Most cited references141

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          Rhythms of the Brain

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            Construction of a genetic toggle switch in Escherichia coli.

            It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy.
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              Bifurcation dynamics in lineage-commitment in bipotent progenitor cells.

              Lineage specification of multipotent progenitor cells is governed by a balance of lineage-affiliated transcription factors, such as GATA1 and PU.1, which regulate the choice between erythroid and myelomonocytic fates. But how ratios of lineage-determining transcription factors stabilize progenitor cells and resolve their indeterminacy to commit them to discrete, mutually exclusive fates remains unexplained. We used a simple model and experimental measurements to analyze the dynamics of a binary fate decision governed by a gene-circuit containing auto-stimulation and cross-inhibition, as embodied by the GATA1-PU.1 paradigm. This circuit generates stable attractors corresponding to erythroid and myelomonocytic fates, as well as an uncommitted metastable state characterized by coexpression of both regulators, explaining the phenomenon of "multilineage priming". GATA1 and PU.1 mRNA and transcriptome dynamics of differentiating progenitor cells confirm that commitment occurs in two stages, as suggested by the model: first, the progenitor state is destabilized in an almost symmetrical bifurcation event, resulting in a poised state at the boundary between the two lineage-specific attractors; second, the cell is driven to the respective, now accessible attractors. This minimal model captures fundamental features of binary cell fate decisions, uniting the concepts of stochastic (selective) and deterministic (instructive) regulation, and hence, may apply to a wider range of binary fate decision points.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: ValidationRole: Writing – review & editing
                Journal
                Interface Focus
                Interface Focus
                RSFS
                royfocus
                Interface Focus
                The Royal Society
                2042-8898
                2042-8901
                April 15, 2022
                6 June 2022
                April 15, 2022
                : 12
                : 3 , Theme issue ‘Time-keeping and decision-making in living cells; Oscillations and Synchronization (Part I)’ organised by Attila Csikasz-Nagy, Didier Gonze, Jae Kyoung Kim, Silvia Santos, John Tyson and Jana Wolf
                : 20210089
                Affiliations
                [ 1 ] Unité de Chronobiologie théorique, Faculté des Sciences, Université Libre de Bruxelles (ULB), , 1050 Brussels, Belgium
                [ 2 ] Center for Systems Biology, School of Mathematical Sciences, Soochow University, , Suzhou, People's Republic of China
                Author notes

                Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.5898409.

                Author information
                http://orcid.org/0000-0002-8371-8119
                Article
                rsfs20210089
                10.1098/rsfs.2021.0089
                9016794
                35450278
                02f445a8-28a8-445b-bb76-1063ae6c6527
                © 2022 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : December 22, 2021
                : March 9, 2022
                Funding
                Funded by: National Natural Science Foundation of China, http://dx.doi.org/10.13039/501100001809;
                Award ID: 11701405
                Award ID: 12071330
                Funded by: Research and Development Program of China;
                Award ID: 2018YFA0801103
                Categories
                1004
                44
                181
                24
                Articles
                Review Articles

                Life sciences
                oscillations,biological rhythms,synchronization,birhythmicity,bistability,computational systems biology

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