ArticlePLoS computational biology2019
The invasion of de-differentiating cancer cells into hierarchical tissues.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- A damage-structured PDE model of stem cell hierarchies: The dual role of dedifferentiation in tissue homeostasis and aging.PloS one · 2026Article
- Negligible Long-Term Impact of Nonlinear Growth Dynamics on Heterogeneity in Models of Cancer Cell Populations.Bulletin of mathematical biology · 2025Article
- Understanding and leveraging phenotypic plasticity during metastasis formation.NPJ systems biology and applications · 2023Article
- Why are cell populations maintained via multiple compartments?Journal of the Royal Society, Interface · 2022Article
- Stem/progenitor cells in normal physiology and disease of the pancreas.Molecular and cellular endocrinology · 2021Review
- Targeting Cancer Stem Cell Markers or Pathways: A Potential Therapeutic Strategy for Oral Cancer Treatment.International journal of stem cells · 2021Review
- MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development.Biomolecules · 2021Review
- The effects of phenotypic plasticity on the fixation probability of mutant cancer stem cells.Journal of theoretical biology · 2020Article
- Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer.Cancers · 2020Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many fast renewing tissues are characterized by a hierarchical cellular architecture, with tissue specific stem cells at the root of the cellular hierarchy, differentiating into a whole range of specialized cells. There is increasing evidence that tumors are structured in a very similar way, mirroring the hierarchical structure of the host tissue. In some tissues, differentiated cells can also revert to the stem cell phenotype, which increases the risk that mutant cells lead to long lasting clones in the tissue. However, it is unclear under which circumstances de-differentiating cells will invade a tissue. To address this, we developed mathematical models to investigate how de-differentiation is selected as an adaptive mechanism in the context of cellular hierarchies. We derive thresholds for which de-differentiation is expected to emerge, and it is shown that the selection of de-differentiation is a result of the combination of the properties of cellular hierarchy and de-differentiation patterns. Our results suggest that de-differentiation is most likely to be favored provided stem cells having the largest effective self-renewal rate. Moreover, jumpwise de-differentiation provides a wider range of favorable conditions than stepwise de-differentiation. Finally, the effect of de-differentiation on the redistribution of self-renewal and differentiation probabilities also greatly influences the selection for de-differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.