ArticleBiology direct2016
The role of cell location and spatial gradients in the evolutionary dynamics of colon and intestinal crypts.
Article in Biology direct, 2016. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed.
- Stochastic model for cell population dynamics quantifies homeostasis in colonic crypts and its disruption in early tumorigenesis.Proceedings. Biological sciences · 2023Article
- Article
- Article
- Data Driven Mathematical Model of Colon Cancer Progression.Journal of clinical medicine · 2020Article
- The relationship between intestinal goblet cells and the immune response.Bioscience reports · 2020Review
- Optimizing homeostatic cell renewal in hierarchical tissues.PLoS computational biology · 2018Article
- Phenotypic heterogeneity in modeling cancer evolution.PloS one · 2017Article
- The role of backward cell migration in two-hit mutants' production in the stem cell niche.PloS one · 2017Article
- Near Equilibrium Calculus of Stem Cells in Application to the Airway Epithelium Lineage.PLoS computational biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColon and intestinal crypts serve as an important model system for adult stem cell proliferation and differentiation. We develop a spatial stochastic model to study the rate of somatic evolution in a normal crypt, focusing on the production of two-hit mutants that inactivate a tumor suppressor gene. We investigate the effect of cell division pattern along the crypt on mutant production, assuming that the division rate of each cell depends on its location.
resultsWe find that higher probability of division at the bottom of the crypt, where the stem cells are located, leads to a higher rate of double-hit mutant production. The optimal case for delaying mutations occurs when most of the cell divisions happen at the top of the crypt. We further consider an optimization problem where the "evolutionary" penalty for double-hit mutant generation is complemented with a "functional" penalty that assures that fully differentiated cells at the top of the crypt cannot divide.
conclusionThe trade-off between the two types of objectives leads to the selection of an intermediate division pattern, where the cells in the middle of the crypt divide with the highest rate. This matches the pattern of cell divisions obtained experimentally in murine crypts. REVIEWERS: This article was reviewed by David Axelrod (nominated by an Editorial Board member, Marek Kimmel), Yang Kuang and Anna Marciniak-Czochra. For the full reviews, please go to the Reviewers' comments section.
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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.