ArticlePloS one2012
Modelling the spatio-temporal cell dynamics reveals novel insights on cell differentiation and proliferation in the small intestinal crypt.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Pooled it
- Organoid Cultures In Silico: Tools or Toys?Bioengineering (Basel, Switzerland) · 2022Review
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- 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
- Antrodin C, an NADPH Dependent Metabolism, Encourages Crosstalk between Autophagy and Apoptosis in Lung Carcinoma Cells by Use of an AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway.Molecules (Basel, Switzerland) · 2019Article
- Chronic TNFα-driven injury delays cell migration to villi in the intestinal epithelium.Journal of the Royal Society, Interface · 2018Article
- On the utility of a compartmental population kinetics model of intestinal epithelial stem cell proliferation and differentiation.Theoretical biology & medical modelling · 2017Article
- The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt.PLoS computational biology · 2017Article
- Cell proliferation within small intestinal crypts is the principal driving force for cell migration on villi.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- The role of backward cell migration in two-hit mutants' production in the stem cell niche.PloS one · 2017Article
- The role of cell location and spatial gradients in the evolutionary dynamics of colon and intestinal crypts.Biology direct · 2016Article
- Design Principles for Engineering of Tissues from Human Pluripotent Stem Cells.Current stem cell reports · 2016Article
- The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth Promotes Robust Intestinal Crypt Structure and Homeostasis.PLoS computational biology · 2015Article
- Investigation of inflammation and tissue patterning in the gut using a Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT).PLoS computational biology · 2014Article
- Unraveling intestinal stem cell behavior with models of crypt dynamics.Integrative biology : quantitative biosciences from nano to macro · 2014Review
- A mathematical model of the colon crypt capturing compositional dynamic interactions between cell types.International journal of experimental pathology · 2014Article
- A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments.Theoretical biology & medical modelling · 2013Article
- Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.PloS one · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
We developed a slow structural relaxation model to describe cellular dynamics in the crypt of the mouse small intestine. Cells are arranged in a three dimensional spiral the size of which dynamically changes according to cell production demands of adjacent villi. Cell differentiation and proliferation is regulated through Wnt and Notch signals, the strength of which depends on the local cell composition. The highest level of Wnt activity is associated with maintaining equipotent stem cells (SC), Paneth cells and common goblet-Paneth cell progenitors (CGPCPs) intermingling at the crypt bottom. Low levels of Wnt signalling area are associated with stem cells giving rise to secretory cells (CGPCPs, enteroendocrine or Tuft cells) and proliferative absorptive progenitors. Deciding between these two fates, secretory and stem/absorptive cells, depends on Notch signalling. Our model predicts that Notch signalling inhibits secretory fate if more than 50% of cells they are in contact with belong to the secretory lineage. CGPCPs under high Wnt signalling will differentiate into Paneth cells while those migrating out from the crypt bottom differentiate into goblet cells. We have assumed that mature Paneth cells migrating upwards undergo anoikis. Structural relaxation explains the localisation of Paneth cells to the crypt bottom in the absence of active forces. The predicted crypt generation time from one SC is 4-5 days with 10-12 days needed to reach a structural steady state. Our predictions are consistent with experimental observations made under altered Wnt and Notch signalling. Mutations affecting stem cells located at the crypt floor have a 50% chance of being propagated throughout the crypt while mutations in cells above are rarely propagated. The predicted recovery time of an injured crypt losing half of its cells is approximately 2 days.
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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.