Heterogeneity of the Level of Activity of Lgr5+ Intestinal Stem Cells

Intestinal stem cells (ISCs) are a group of rare cells located in the intestinal crypts which are responsible for the maintenance of the intestinal epithelial homeostasis and regeneration following injury or inflammation. Lineage tracing experiments in mice have proven that ISCs can repopulate the entire intestinal crypt. It is noteworthy that in such experiments, only a subset of intestinal crypts is marked by the specific marker. This is suggestive of different levels of activity of stem cells in different crypts i.e. intracryptal variation. Niche succession i.e. dominating the entire crypt by the progenies of one stem cell is also suggestive of the intercryptal stem cell heterogeneity. Regional differences in crypt size, proliferative index, and distribution of proliferative cells along the crypt axis have been reported. It is conceivable that ISCs are heterogeneous in terms of their levels of activity. Appreciation of such heterogeneity will significantly challenge the way in which ISCs are investigated. A better understanding of ISC biology will in turn improve our mechanistic understanding of major intestinal disease including inflammatory bowel disease and colorectal cancer.