Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability.
Phenotypic evolutionary models have been used with great success in many areas of biology, but thus far have not been applied to the study of stem cells except for investigations of cancer. We develop a framework that allows such modeling techniques to be applied to stem cells more generally. The fu...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2217616?pdf=render |
| _version_ | 1828371231142838272 |
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| author | Marc Mangel Michael B Bonsall |
| author_facet | Marc Mangel Michael B Bonsall |
| author_sort | Marc Mangel |
| collection | DOAJ |
| description | Phenotypic evolutionary models have been used with great success in many areas of biology, but thus far have not been applied to the study of stem cells except for investigations of cancer. We develop a framework that allows such modeling techniques to be applied to stem cells more generally. The fundamental modeling structure is the stochastic kinetics of stem cells in their niche and of transit amplifying and fully differentiated cells elsewhere in the organism, with positive and negative feedback. This formulation allows graded signals to be turned into all or nothing responses, and shows the importance of looking beyond the niche for understanding how stem cells behave. Using the deterministic version of this framework, we show how competition between different stem cell lines can be analyzed, and under what circumstances stem cells in a niche will be replaced by other stem cells with different phenotypic characteristics. Using the stochastic version of our framework and state dependent life history theory, we show that the optimal behavior of a focal stem cell will involve long periods of quiescence and that a population of identical stem cells will show great variability in the times at which activity occurs; we compare our results with classic ones on quiescence and variability in the hematopoietic system. |
| first_indexed | 2024-04-14T06:47:39Z |
| format | Article |
| id | doaj.art-67fad80e671047c08c4f14c246ebd740 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T06:47:39Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-67fad80e671047c08c4f14c246ebd7402022-12-22T02:07:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0132e159110.1371/journal.pone.0001591Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability.Marc MangelMichael B BonsallPhenotypic evolutionary models have been used with great success in many areas of biology, but thus far have not been applied to the study of stem cells except for investigations of cancer. We develop a framework that allows such modeling techniques to be applied to stem cells more generally. The fundamental modeling structure is the stochastic kinetics of stem cells in their niche and of transit amplifying and fully differentiated cells elsewhere in the organism, with positive and negative feedback. This formulation allows graded signals to be turned into all or nothing responses, and shows the importance of looking beyond the niche for understanding how stem cells behave. Using the deterministic version of this framework, we show how competition between different stem cell lines can be analyzed, and under what circumstances stem cells in a niche will be replaced by other stem cells with different phenotypic characteristics. Using the stochastic version of our framework and state dependent life history theory, we show that the optimal behavior of a focal stem cell will involve long periods of quiescence and that a population of identical stem cells will show great variability in the times at which activity occurs; we compare our results with classic ones on quiescence and variability in the hematopoietic system.http://europepmc.org/articles/PMC2217616?pdf=render |
| spellingShingle | Marc Mangel Michael B Bonsall Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability. PLoS ONE |
| title | Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability. |
| title_full | Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability. |
| title_fullStr | Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability. |
| title_full_unstemmed | Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability. |
| title_short | Phenotypic evolutionary models in stem cell biology: replacement, quiescence, and variability. |
| title_sort | phenotypic evolutionary models in stem cell biology replacement quiescence and variability |
| url | http://europepmc.org/articles/PMC2217616?pdf=render |
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