ArticleTheoretical biology & medical modelling2017
On the utility of a compartmental population kinetics model of intestinal epithelial stem cell proliferation and differentiation.
Article in Theoretical biology & medical modelling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium.Nature communications · 2021Article
- Systems Modeling to Quantify Safety Risks in Early Drug Development: Using Bifurcation Analysis and Agent-Based Modeling as Examples.The AAPS journal · 2021Review
- Identification of influential proteins in the classical retinoic acid signaling pathway.Theoretical biology & medical modelling · 2018Article
- Chronic TNFα-driven injury delays cell migration to villi in the intestinal epithelium.Journal of the Royal Society, Interface · 2018Article
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1 author at 1 institution in 1 country.
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Abstract
backgroundThe small intestinal epithelium is a dynamic system with specialized cell types. The various cell populations of this tissue are continually renewed and replenished from stem cells that reside in the small intestinal crypt. The cell types and their locations in the crypt and villus are well known, but the details of the kinetics of stem cell division, and precursor cell proliferation and differentiation into mature enterocytes and secretory cells are still being studied. These proliferation and differentiation events have been extensively modeled with a variety of computational approaches in the past.
methodsA compartmental population kinetics model, incorporating experimentally measured proliferation rates for various intestinal epithelial cell types, is implemented for a previously reported scheme for the intestinal cell dynamics. A sensitivity analysis is performed to determine the effect that varying the model parameters has upon the model outputs, the steady-state cell populations.
resultsThe model is unable to reproduce the experimentally known timescale of renewal of the intestinal epithelium if literature values for the proliferation rates of stem cells and transit amplifying cells are employed. Unphysically large rates of proliferation result when these parameters are allowed to vary to reproduce this timescale and the steady-state populations of terminally differentiated intestinal epithelial cells. Sensitivity analysis reveals that the strongest contributor to the steady-state populations is the transit amplifying cell proliferation rate when literature values are used, but that the differentiation rate of transit amplifying cells to secretory progenitor cells dominates when all parameters are allowed to vary.
conclusionsA compartmental population kinetics model of proliferation and differentiation of cells of the intestinal epithelium can provide a simplifying means of understanding a complicated multistep process. However, when literature values for proliferation rates of the crypt based columnar and transit amplifying cell populations are employed in the model, it cannot reproduce the experimentally known timescale of intestinal epithelial renewal. Nevertheless, it remains a valuable conceptual tool, and its sensitivity analysis provides important clues for which events in the process are the most important in controlling the steady-state populations of specialized intestinal epithelial cells.
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