Gastrointestinal Stem Cells

Abstract

In the gastrointestinal (GI) epithelium, cellular differentiation occurs in five stages: stem cells, precursor cells, transit cells, mature cells, and terminal cells. Stem cells are the least differentiated and have the greatest proliferation potential. In the stomach, they are located in the isthmus region of the pit-gland unit and give rise to four main cell lineages through precursor-amplifying cells: pre-pit cells give rise to mucous-secreting pit cells that migrate and reach the gastric luminal surface in 3 d; pre-neck cells differentiate into neck cells that migrate toward the bottom of the gland while changing their phenotype into the longest lived cells in the unit, zymogenic cells; pre-parietal cells complete their differentiation in the isthmus and then undergo bipolar migration to the pit and the base of the gland, where they have a life-span of about 2 mo. The precursors of enteroendocrine cells also originate in the isthmus and follow the bipolar mode of migration. In the small intestine, stem cells are located in the fourth cell layer from the crypt bottom and are derived from a single preceding cell (clonal). An adult mouse has about 1.1 million crypts and each crypt contains about 250 cells, of which about two-thirds go through the cell cycle every 12 h; each crypt produces about 13–16 new cells per hour! They give rise to four main cell lineages: absorptive, goblet, enteroendocrine, and Paneth. While members of the former three lineages differentiate while migrating upward along the crypt-villus axis, those of the latter complete their differentiation and remain at the crypt bottom. M-cell precursors are found in the intestinal crypts around lymphoid follicles and their mature forms migrate to cover the dome-shaped Peyer’s patches. In the colon, the lineages are columnar cells (80%), goblet cells (16%), deep crypt secretory cells (3%), and enteroendocrine cells (0.4%). Precursors of caveolated cells are also produced by stem cells throughout the GI tract.