ArticlePLoS computational biology2011
Dynamics of mutant cells in hierarchical organized tissues.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Negligible Long-Term Impact of Nonlinear Growth Dynamics on Heterogeneity in Models of Cancer Cell Populations.Bulletin of mathematical biology · 2025Article
- Stochastic journeys of cell progenies through compartments and the role of self-renewal, symmetric and asymmetric division.Scientific reports · 2024Article
- Adult stem cell activity in naked mole rats for long-term tissue maintenance.Nature communications · 2023Article
- The structure of the hematopoietic system can explain chronic myeloid leukemia progression.Scientific reports · 2023Article
- Why are cell populations maintained via multiple compartments?Journal of the Royal Society, Interface · 2022Article
- Trade-off between reducing mutational accumulation and increasing commitment to differentiation determines tissue organization.Nature communications · 2022Article
- Memory shapes microbial populations.PLoS computational biology · 2021Article
- A systems pharmacology model for gene therapy in sickle cell disease.CPT: pharmacometrics & systems pharmacology · 2021Article
- Article
- Effect of feedback regulation on stem cell fractions in tissues and tumors: Understanding chemoresistance in cancer.Journal of theoretical biology · 2021Article
- Inferring Tumor Proliferative Organization from Phylogenetic Tree Measures in a Computational Model.Systematic biology · 2020Article
- Differentiation of leukemic blasts is not completely blocked in acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The invasion of de-differentiating cancer cells into hierarchical tissues.PLoS computational biology · 2019Article
- Replicative cellular age distributions in compartmentalized tissues.Journal of the Royal Society, Interface · 2018Article
- Effect of cellular de-differentiation on the dynamics and evolution of tissue and tumor cells in mathematical models with feedback regulation.Journal of theoretical biology · 2018Article
- Variation of mutational burden in healthy human tissues suggests non-random strand segregation and allows measuring somatic mutation rates.PLoS computational biology · 2018Article
- Evolutionary dynamics of paroxysmal nocturnal hemoglobinuria.PLoS computational biology · 2018Article
- Optimizing homeostatic cell renewal in hierarchical tissues.PLoS computational biology · 2018Article
- A stochastic model of myeloid cell lineages in hematopoiesis and pathway mutations in acute myeloid leukemia.PloS one · 2018Article
- Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations.Nature communications · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
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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