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Transient hysteresis and inherent stochasticity in gene regulatory networks
Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes bistability and hysteresis, which enables the pe...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783536/ https://www.ncbi.nlm.nih.gov/pubmed/31594925 http://dx.doi.org/10.1038/s41467-019-12344-w |
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author | Pájaro, M. Otero-Muras, I. Vázquez, C. Alonso, A. A. |
author_facet | Pájaro, M. Otero-Muras, I. Vázquez, C. Alonso, A. A. |
author_sort | Pájaro, M. |
collection | PubMed |
description | Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes bistability and hysteresis, which enables the persistence of the acquired cellular state after withdrawal of the stimulus, ensuring a robust cellular response. However, stochasticity inherent to gene expression dynamics is not compatible with hysteresis, since the stationary solution of the governing Chemical Master Equation does not depend on the initial conditions. We provide a quantitative description of a transient hysteresis phenomenon reconciling experimental evidence of hysteretic behaviour in gene regulatory networks with inherent stochasticity: under sufficiently slow dynamics hysteresis is transient. We quantify this with an estimate of the convergence rate to the equilibrium and introduce a natural landscape capturing system’s evolution that, unlike traditional cell fate potential landscapes, is compatible with coexistence at the microscopic level. |
format | Online Article Text |
id | pubmed-6783536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67835362019-10-10 Transient hysteresis and inherent stochasticity in gene regulatory networks Pájaro, M. Otero-Muras, I. Vázquez, C. Alonso, A. A. Nat Commun Article Cell fate determination, the process through which cells commit to differentiated states is commonly mediated by gene regulatory motifs with mutually exclusive expression states. The classical deterministic picture for cell fate determination includes bistability and hysteresis, which enables the persistence of the acquired cellular state after withdrawal of the stimulus, ensuring a robust cellular response. However, stochasticity inherent to gene expression dynamics is not compatible with hysteresis, since the stationary solution of the governing Chemical Master Equation does not depend on the initial conditions. We provide a quantitative description of a transient hysteresis phenomenon reconciling experimental evidence of hysteretic behaviour in gene regulatory networks with inherent stochasticity: under sufficiently slow dynamics hysteresis is transient. We quantify this with an estimate of the convergence rate to the equilibrium and introduce a natural landscape capturing system’s evolution that, unlike traditional cell fate potential landscapes, is compatible with coexistence at the microscopic level. Nature Publishing Group UK 2019-10-08 /pmc/articles/PMC6783536/ /pubmed/31594925 http://dx.doi.org/10.1038/s41467-019-12344-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Pájaro, M. Otero-Muras, I. Vázquez, C. Alonso, A. A. Transient hysteresis and inherent stochasticity in gene regulatory networks |
title | Transient hysteresis and inherent stochasticity in gene regulatory networks |
title_full | Transient hysteresis and inherent stochasticity in gene regulatory networks |
title_fullStr | Transient hysteresis and inherent stochasticity in gene regulatory networks |
title_full_unstemmed | Transient hysteresis and inherent stochasticity in gene regulatory networks |
title_short | Transient hysteresis and inherent stochasticity in gene regulatory networks |
title_sort | transient hysteresis and inherent stochasticity in gene regulatory networks |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783536/ https://www.ncbi.nlm.nih.gov/pubmed/31594925 http://dx.doi.org/10.1038/s41467-019-12344-w |
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