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A Branching Process to Characterize the Dynamics of Stem Cell Differentiation

The understanding of the regulatory processes that orchestrate stem cell maintenance is a cornerstone in developmental biology. Here, we present a mathematical model based on a branching process formalism that predicts average rates of proliferative and differentiative divisions in a given stem cell...

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Autor principal: Míguez, David G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541069/
https://www.ncbi.nlm.nih.gov/pubmed/26286123
http://dx.doi.org/10.1038/srep13265
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author Míguez, David G.
author_facet Míguez, David G.
author_sort Míguez, David G.
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description The understanding of the regulatory processes that orchestrate stem cell maintenance is a cornerstone in developmental biology. Here, we present a mathematical model based on a branching process formalism that predicts average rates of proliferative and differentiative divisions in a given stem cell population. In the context of vertebrate neurogenesis, the model predicts complex non-monotonic variations in the rates of pp, pd and dd modes of division as well as in cell cycle length, in agreement with experimental results. Moreover, the model shows that the differentiation probability follows a binomial distribution, allowing us to develop equations to predict the rates of each mode of division. A phenomenological simulation of the developing spinal cord informed with the average cell cycle length and division rates predicted by the mathematical model reproduces the correct dynamics of proliferation and differentiation in terms of average numbers of progenitors and differentiated cells. Overall, the present mathematical framework represents a powerful tool to unveil the changes in the rate and mode of division of a given stem cell pool by simply quantifying numbers of cells at different times.
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spelling pubmed-45410692015-08-31 A Branching Process to Characterize the Dynamics of Stem Cell Differentiation Míguez, David G. Sci Rep Article The understanding of the regulatory processes that orchestrate stem cell maintenance is a cornerstone in developmental biology. Here, we present a mathematical model based on a branching process formalism that predicts average rates of proliferative and differentiative divisions in a given stem cell population. In the context of vertebrate neurogenesis, the model predicts complex non-monotonic variations in the rates of pp, pd and dd modes of division as well as in cell cycle length, in agreement with experimental results. Moreover, the model shows that the differentiation probability follows a binomial distribution, allowing us to develop equations to predict the rates of each mode of division. A phenomenological simulation of the developing spinal cord informed with the average cell cycle length and division rates predicted by the mathematical model reproduces the correct dynamics of proliferation and differentiation in terms of average numbers of progenitors and differentiated cells. Overall, the present mathematical framework represents a powerful tool to unveil the changes in the rate and mode of division of a given stem cell pool by simply quantifying numbers of cells at different times. Nature Publishing Group 2015-08-19 /pmc/articles/PMC4541069/ /pubmed/26286123 http://dx.doi.org/10.1038/srep13265 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Míguez, David G.
A Branching Process to Characterize the Dynamics of Stem Cell Differentiation
title A Branching Process to Characterize the Dynamics of Stem Cell Differentiation
title_full A Branching Process to Characterize the Dynamics of Stem Cell Differentiation
title_fullStr A Branching Process to Characterize the Dynamics of Stem Cell Differentiation
title_full_unstemmed A Branching Process to Characterize the Dynamics of Stem Cell Differentiation
title_short A Branching Process to Characterize the Dynamics of Stem Cell Differentiation
title_sort branching process to characterize the dynamics of stem cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541069/
https://www.ncbi.nlm.nih.gov/pubmed/26286123
http://dx.doi.org/10.1038/srep13265
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