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22 Stem Cells in the Epithelium of the Small Intestine and Colon

Douglas J. Winton


The inner lining of the colon and small intestine is a simple columnar epithelium that is constantly renewed by cellular migration from pockets of proliferative activity or crypts. Small intestinal cells leave the crypt and migrate onto villi that protrude into the gut lumen. Only at the point of exit from the crypt do villus epithelial cells become fully mature with respect to biochemical markers of differentiation. These cells are principally epithelial columnar cells, goblet cells, and enteroendocrine cells. Within the crypt, immature proliferative forms are morphologically identifiable as being precursors to these mature cell types. Near the crypt base, immature cells lacking the morphological characteristics of mature types are found and coexist with a fourth differentiated cell type, the Paneth cell (Fig. 1). These features present as a gradient with progressively higher positions being associated with a more developed morphological appearance. Cell kinetic experiments have determined the cycling characteristics of epithelial cells within the crypt, the time of appearance of identifiable differentiated cells from proliferative precursors, and the turnover times of crypt and villus populations. Studies of this kind, in both small intestine and colon, analyzed as a function of cellular position within the crypt (from position 1 at the crypt base), have led to the central tenet of gut stem cell biology: that cells originate from, and therefore stem cells reside near, the crypt base (Fig. 2). Proliferating cells at higher locations in the crypt may have the potential to divide 1, 2, 3, 4, and possibly 5...

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