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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2015
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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. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-4541069 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT miguezdavidg abranchingprocesstocharacterizethedynamicsofstemcelldifferentiation AT miguezdavidg branchingprocesstocharacterizethedynamicsofstemcelldifferentiation |