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Modeling the clonal heterogeneity of stem cells
Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998476/ https://www.ncbi.nlm.nih.gov/pubmed/21083923 http://dx.doi.org/10.1186/1742-4682-7-44 |
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author | Tuck, David P Miranker, Willard |
author_facet | Tuck, David P Miranker, Willard |
author_sort | Tuck, David P |
collection | PubMed |
description | Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, apoptosis, and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework, we propose a method to devise an optimal strategy of treatments to regulate expansion, contraction, or mutual maintenance of cells with specific properties. |
format | Text |
id | pubmed-2998476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29984762011-01-05 Modeling the clonal heterogeneity of stem cells Tuck, David P Miranker, Willard Theor Biol Med Model Research Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, apoptosis, and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework, we propose a method to devise an optimal strategy of treatments to regulate expansion, contraction, or mutual maintenance of cells with specific properties. BioMed Central 2010-11-17 /pmc/articles/PMC2998476/ /pubmed/21083923 http://dx.doi.org/10.1186/1742-4682-7-44 Text en Copyright ©2010 Tuck and Miranker; 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 Tuck, David P Miranker, Willard Modeling the clonal heterogeneity of stem cells |
title | Modeling the clonal heterogeneity of stem cells |
title_full | Modeling the clonal heterogeneity of stem cells |
title_fullStr | Modeling the clonal heterogeneity of stem cells |
title_full_unstemmed | Modeling the clonal heterogeneity of stem cells |
title_short | Modeling the clonal heterogeneity of stem cells |
title_sort | modeling the clonal heterogeneity of stem cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998476/ https://www.ncbi.nlm.nih.gov/pubmed/21083923 http://dx.doi.org/10.1186/1742-4682-7-44 |
work_keys_str_mv | AT tuckdavidp modelingtheclonalheterogeneityofstemcells AT mirankerwillard modelingtheclonalheterogeneityofstemcells |