Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.
- Author(s)
- van der Wath, RC; Gardiner, BS; Burgess, AW; Smith, DW;
- Details
- Publication Year 2013,Volume 8,Issue #9,Page e73204
- Journal Title
- PLoS One
- Publication Type
- Journal Article
- Abstract
- The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits) spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2-3 days in mice (3-5 days in humans) and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the 'pedigree' and the 'niche' models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.
- Publisher
- Public Library of Science
- Keywords
- Stem cell niche ; Simulation and modeling ; Ecological niches ; Agent-based modeling ; Stem cells ;Cell migration ;Cell differentiation ;Cell cycle and cell division
- Research Division(s)
- Structural Biology
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0073204
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771985/- Terms of Use/Rights Notice
- Copyright: © 2013 van der Wath et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creation Date: 2013-01-01 12:00:00