Fig. 1

The intestinal epithelium. (a) The intestinal lining consists of an epithelial monolayer covering invaginations (crypts) and finger like protrusions (villi, only in the small intestine). Intestinal stem cells (ISC) reside in the bottom of the crypts, absorptive and secretory progenitor cells directly above the ISC zone, and more differentiated cells towards the top of crypts and on the villi. Intestinal progenitor and differentiated cells move upwards due to the massive tissue renewal fueled by the ISCs. This is a continuous process and it only takes several days before differentiated cells undergo apoptosis and are shed into the gut lumen. (b) The ISC compartment is sensitive to cytotoxic injury, such as irradiation. Consequently, upon DNA damage ISCs undergo apoptosis. The progenitor cells located higher up in the crypt replace the loss of ISCs and due to the new topological position regain niche signals, which then install ISC activity. Therefore, the ISC compartment is a dynamic population and progenitor- and potentially fully differentiated cells, show an enormous cellular plasticity upon ISC loss