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Novel generic models for differentiating stem cells reveal oscillatory mechanisms

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddin...

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Detalles Bibliográficos
Autores principales: Farjami, Saeed, Camargo Sosa, Karen, Dawes, Jonathan H. P., Kelsh, Robert N., Rocco, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492175/
https://www.ncbi.nlm.nih.gov/pubmed/34610261
http://dx.doi.org/10.1098/rsif.2021.0442
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author Farjami, Saeed
Camargo Sosa, Karen
Dawes, Jonathan H. P.
Kelsh, Robert N.
Rocco, Andrea
author_facet Farjami, Saeed
Camargo Sosa, Karen
Dawes, Jonathan H. P.
Kelsh, Robert N.
Rocco, Andrea
author_sort Farjami, Saeed
collection PubMed
description Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.
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spelling pubmed-84921752021-11-03 Novel generic models for differentiating stem cells reveal oscillatory mechanisms Farjami, Saeed Camargo Sosa, Karen Dawes, Jonathan H. P. Kelsh, Robert N. Rocco, Andrea J R Soc Interface Life Sciences–Mathematics interface Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process. The Royal Society 2021-10-06 /pmc/articles/PMC8492175/ /pubmed/34610261 http://dx.doi.org/10.1098/rsif.2021.0442 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Life Sciences–Mathematics interface
Farjami, Saeed
Camargo Sosa, Karen
Dawes, Jonathan H. P.
Kelsh, Robert N.
Rocco, Andrea
Novel generic models for differentiating stem cells reveal oscillatory mechanisms
title Novel generic models for differentiating stem cells reveal oscillatory mechanisms
title_full Novel generic models for differentiating stem cells reveal oscillatory mechanisms
title_fullStr Novel generic models for differentiating stem cells reveal oscillatory mechanisms
title_full_unstemmed Novel generic models for differentiating stem cells reveal oscillatory mechanisms
title_short Novel generic models for differentiating stem cells reveal oscillatory mechanisms
title_sort novel generic models for differentiating stem cells reveal oscillatory mechanisms
topic Life Sciences–Mathematics interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492175/
https://www.ncbi.nlm.nih.gov/pubmed/34610261
http://dx.doi.org/10.1098/rsif.2021.0442
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