The small intestinal epithelium forms crypt and villus structures overlying the lamina propria (left) whereas the colonic epithelium only has crypts (right).
Active cycling intestinal stem cells (ISCs) are located within the crypt base (red). Paneth cells (yellow) are only found in the small intestine. Under homeostatic conditions, ISCs divide via a neutral drift process to generate either two ISCs or two cells that enter the transit-amplifying population (purple) which maintain a limited capacity to divide prior to maturation into secretory or absorptive lineages [5,19]. Cells (other than ISCs and Paneth cells which are longer lived and remain in the crypt base) undergo a process of migration and differentiation along the crypt-villus axis (black arrow). Once epithelial cells reach the villus tip in the small intestine or inter-crypt table in the colon, they undergo apoptosis and are shed into the lumen. Neighbouring cells reform tight junctions beneath the shedding cell to ensure the intestinal epithelial barrier is maintained throughout the extrusion process [5,92,108]. The process from ISC division at the crypt base to apoptosis and cell shedding at the villus tip takes 3–5 days depending on species and location along the cephalocaudal axis [109].