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          Institute: MPI für Evolutionsbiologie     Collection: Research Group Evolutionary Theory     Display Documents

ID: 578932.0, MPI für Evolutionsbiologie / Research Group Evolutionary Theory
Dynamics of mutant cells in hierarchical organized tissues
Authors:Werner, Benjamin; Dingli, David; Lenaerts, Tom; Pacheco, Jorge M.; Traulsen, Arne
Date of Publication (YYYY-MM-DD):2011-12-01
Title of Journal:PLoS Computational Biology
Issue / Number:12
Sequence Number of Article:e1002290
Review Status:not specified
Audience:Not Specified
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Communicated by:Brigitte Lechner
Affiliations:MPI für Evolutionsbiologie/AG Evolutionstheorie
External Affiliations:Division of Hematology, Mayo Clinic, College of Medicine, Rochester, Minnesota, United States of America; MLG, Département d’Informatique, Université Libre de Bruxelles, Brussels, Belgium; AI-LAB Computer Science Department, Vrije
Universiteit Brussel, Brussels, Belgium; Departmento de Matemática e Aplicacões, Universidade do Minho, Braga, Portugal; ATP-group, CMAF, Lisboa, Portugal
Identifiers:ISSN:1553-734X (print) [ID-No:1]
ISSN:1553-7358 (online) [ID-No:2]
DOI:10.1371/journal.pcbi.1002290 [ID-No:3]
LOCALID:2889/S 39234 [Listen-Nummer/S-Nummer]
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