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Bridging time scales in cellular decision making with a stochastic bistable switch
BACKGROUND: Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. Some of these transformations act over a very long time scale on the cell population level, up to the entire lifespan of the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247078/ https://www.ncbi.nlm.nih.gov/pubmed/20696063 http://dx.doi.org/10.1186/1752-0509-4-108 |
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author | Waldherr, Steffen Wu, Jingbo Allgöwer, Frank |
author_facet | Waldherr, Steffen Wu, Jingbo Allgöwer, Frank |
author_sort | Waldherr, Steffen |
collection | PubMed |
description | BACKGROUND: Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. Some of these transformations act over a very long time scale on the cell population level, up to the entire lifespan of the organism. RESULTS: In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. CONCLUSIONS: Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale. |
format | Online Article Text |
id | pubmed-3247078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32470782011-12-30 Bridging time scales in cellular decision making with a stochastic bistable switch Waldherr, Steffen Wu, Jingbo Allgöwer, Frank BMC Syst Biol Research Article BACKGROUND: Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. Some of these transformations act over a very long time scale on the cell population level, up to the entire lifespan of the organism. RESULTS: In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. CONCLUSIONS: Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale. BioMed Central 2010-08-09 /pmc/articles/PMC3247078/ /pubmed/20696063 http://dx.doi.org/10.1186/1752-0509-4-108 Text en Copyright ©2010 Waldherr et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Waldherr, Steffen Wu, Jingbo Allgöwer, Frank Bridging time scales in cellular decision making with a stochastic bistable switch |
title | Bridging time scales in cellular decision making with a stochastic bistable switch |
title_full | Bridging time scales in cellular decision making with a stochastic bistable switch |
title_fullStr | Bridging time scales in cellular decision making with a stochastic bistable switch |
title_full_unstemmed | Bridging time scales in cellular decision making with a stochastic bistable switch |
title_short | Bridging time scales in cellular decision making with a stochastic bistable switch |
title_sort | bridging time scales in cellular decision making with a stochastic bistable switch |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247078/ https://www.ncbi.nlm.nih.gov/pubmed/20696063 http://dx.doi.org/10.1186/1752-0509-4-108 |
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