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.
Highlights
Many tissues, such as skin and blood, undergo constant regeneration
Our definition of a ‘pedigree model’ has immortal cells identified as stem cells and a fixed number of cell divisions by a TA cell before it differentiates into a mature cell
Computational modelling can enhance the understanding of the mechanisms by which cell organisation in the crypt is achieved, as we have shown
Summary
Many tissues, such as skin and blood, undergo constant regeneration This self-renewal is accomplished by millions of cells that divide and differentiate to replenish lost functional cells, or to repair the tissue following injury. The intestinal epithelium exists in a challenging chemical and mechanical environment [5]. This single layer of cells is responsible for both absorption of water and nutrients as well as forming a protective cell-sheet that prevents harmful substances freely entering the lamina propria. The LI studies revealed a distinct ordering along the crypt among proliferative cells at the crypt base and mature cells at the crypt orifice, an observation confirmed by more recent Ki67 immunostaining (a marker for cell proliferation) [10,11]. The Ki67 immunostains further suggest that there exists a fairly sharp boundary between the proliferative and mature regions along the crypt and that proliferative cells primarily occupy the lower third of the crypt
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
