Defining the relationship between stem and progenitor cells in the intestinal epithelium
The intestinal epithelium is maintained by a population of stem cells that are restricted to the base of glandular crypts. At the crypt base there is considerable heterogeneity in the behaviour of cells and in expression of phenotypic markers that associate with stem cell self-renewal. The relative self-renewing activity of any given subset of cells may vary in health and disease. For these reasons we attempt to treat the cells of the lower crypt as a community and to understand self-renewal in terms of overarching behaviours. This is achieved largely in mouse models by establishing the rules governing clonal dynamics by which long-lived clones arise and undergo expansions to populate entire crypts. With these rules established there a number of applications that allow both fundamental biological questions to be addressed such as defining the distinction between stem cells and their more committed daughters. Further to develop approaches to similar analyses in patients with a view to understanding stem cell defects in disease.
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