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The Small Intestine: The Most Rapidly Dividing Tissue of the Body

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Small intestine is the most rapidly dividing tissue of the body. It undergoes a fast turnover of 3-5 days by Intestinal Stem Cells (ISCs), replacing all the older cells with new ones which is necessary for the nutritional uptake by intestinal cells and thereby, maintaining tissue homeostasis. Small intestinal epithelium has several crypts/villi structures which inhabits ISCs. Cells are arranged in the order of increasing maturity from bottom to top of each crypt. ISCs are present at base of each crypt and they give rise to transit-amplifying cells (TA).These transit-amplifying cells divide actively 4-5 times, approximately after every 12 hours. Further, these cells differentiate to form – enterocytes, goblet cells and entroendocrine cells. ISCs differentiate to form Paneth cells towards the base of crypt (Marshman et al., 2002).
ISCs were first identified by BrDU label retention method (Cheng and Leblond, 1974). After 30 years, Clevers and colleagues identified ISCs at single cell resolution by lineage tracing. They found that Lgr5 gene, encoding the leucine-rich repeat-containing G-protein coupled receptor 5, is expressed in ISCs and LGR5+ cells give rise to all four different kind of intestinal epithelial cells (Barker et al., 2007).In addition, LGR5+ cells cultured in vitro give rise to organoid expressing all the markers of intestinal epithelium (Sato et al., 2009). Potential stem cell niche for ISCs consist of Paneth cells, dispersed in between ISCs. In vitro, growth

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