ArticleJournal of the Royal Society, Interface2013
A deterministic model for the occurrence and dynamics of multiple mutations in hierarchically organized tissues.
Article in Journal of the Royal Society, Interface, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 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
- Integration of Immune Cell-Target Cell Conjugate Dynamics Changes the Time Scale of Immune Control of Cancer.Bulletin of mathematical biology · 2025Article
- Dynamically adjusted cell fate decisions and resilience to mutant invasion during steady-state hematopoiesis revealed by an experimentally parameterized mathematical model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stochastic journeys of cell progenies through compartments and the role of self-renewal, symmetric and asymmetric division.Scientific reports · 2024Article
- 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
- Constrained optimization of divisional load in hierarchically organized tissues during homeostasis.Journal of the Royal Society, Interface · 2022Article
- A compartment size-dependent selective threshold limits mutation accumulation in hierarchical tissues.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Modeling and Analyzing Stem-Cell Therapy toward Cancer: Evolutionary Game Theory Perspective.Iranian journal of public health · 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
- A structured population model of clonal selection in acute leukemias with multiple maturation stages.Journal of mathematical biology · 2019Article
- The invasion of de-differentiating cancer cells into hierarchical tissues.PLoS computational biology · 2019Article
- Estimating the number of genetic mutations (hits) required for carcinogenesis based on the distribution of somatic mutations.PLoS computational biology · 2019Article
- Replicative cellular age distributions in compartmentalized tissues.Journal of the Royal Society, Interface · 2018Article
- Optimizing homeostatic cell renewal in hierarchical tissues.PLoS computational biology · 2018Article
- Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments.PLoS computational biology · 2017Article
- Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations.Nature communications · 2017Article
- The role of backward cell migration in two-hit mutants' production in the stem cell niche.PloS one · 2017Article
- Phenotypic heterogeneity in modeling cancer evolution.PloS one · 2017Article
- Emergence of heterogeneity in acute leukemias.Biology direct · 2016Article
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3 authors.
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Abstract
Cancers are rarely caused by single mutations, but often develop as a result of the combined effects of multiple mutations. For most cells, the number of possible cell divisions is limited because of various biological constraints, such as progressive telomere shortening, cell senescence cascades or a hierarchically organized tissue structure. Thus, the risk of accumulating cells carrying multiple mutations is low. Nonetheless, many diseases are based on the accumulation of such multiple mutations. We model a general, hierarchically organized tissue by a multi-compartment approach, allowing any number of mutations within a cell. We derive closed solutions for the deterministic clonal dynamics and the reproductive capacity of single clones. Our results hold for the average dynamics in a hierarchical tissue characterized by an arbitrary combination of proliferation parameters. We show that hierarchically organized tissues strongly suppress cells carrying multiple mutations and derive closed solutions for the expected size and diversity of clonal populations founded by a single mutant within the hierarchy. We discuss the example of childhood acute lymphoblastic leukaemia in detail and find good agreement between our predicted results and recently observed clonal diversities in patients. This result can contribute to the explanation of very diverse mutation profiles observed by whole genome sequencing of many different cancers.
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