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  Dynamics of mutant cells in hierarchical organized tissues

Werner, B., Dingli, D., Lenaerts, T., Pacheco, J. M., & Traulsen, A. (2011). Dynamics of mutant cells in hierarchical organized tissues. PLoS Computational Biology, 7(12): e1002290. doi:10.1371/journal.pcbi.1002290.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-D379-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-D37A-1
Genre: Journal Article

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 Creators:
Werner, Benjamin1, Author              
Dingli, David, Author
Lenaerts, Tom, Author
Pacheco, Jorge M., Author
Traulsen, Arne1, Author              
Affiliations:
1Research Group Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              

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 Abstract: Most tissues in multicellular organisms are maintained by continuous cell renewal processes. However, high turnover of many cells implies a large number of error-prone cell divisions. Hierarchical organized tissue structures with stem cell driven cell differentiation provide one way to prevent the accumulation of mutations, because only few stem cells are long lived. We investigate the deterministic dynamics of cells in such a hierarchical multi compartment model, where each compartment represents a certain stage of cell differentiation. The dynamics of the interacting system is described by ordinary differential equations coupled across compartments. We present analytical solutions for these equations, calculate the corresponding extinction times and compare our results to individual based stochastic simulations. Our general compartment structure can be applied to different tissues, as for example hematopoiesis, the epidermis, or colonic crypts. The solutions provide a description of the average time development of stem cell and non stem cell driven mutants and can be used to illustrate general and specific features of the dynamics of mutant cells in such hierarchically structured populations. We illustrate one possible application of this approach by discussing the origin and dynamics of PIG-A mutant clones that are found in the bloodstream of virtually every healthy adult human. From this it is apparent, that not only the occurrence of a mutant but also the compartment of origin is of importance.

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Language(s): eng - English
 Dates: 2011-12-01
 Publication Status: Published in print
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 Identifiers: eDoc: 578932
DOI: 10.1371/journal.pcbi.1002290
Other: 2889/S 39234
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Title: PLoS Computational Biology
Source Genre: Journal
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Pages: - Volume / Issue: 7 (12) Sequence Number: e1002290 Start / End Page: - Identifier: ISSN: 1553-734X (print)
ISSN: 1553-7358 (online)