Fig. 1.

Intestinal stem cell (ISC) compartments in the mammalian intestine. a The intestinal crypt-villus unit. ISCs reside at the base of the crypt, either in the +4 position counting from the bottom of the crypt (brown) directly above the Paneth cells (gray), or as crypt base columnar (CBC) cells (red) located between the Paneth cells, whereas transit-amplifying (TA) progenitor cells (yellow) can arise from self-renewing CBCs. Goblet cells and enterocytes are labeled purple and green, respectively. b Chemical and immunohistochemical detection of the four principal cell lineages of the small intestine: villus-associated absorptive cells (Fatty acid binding protein, stains the villi), Goblet cells (stained by periodic acid/Schiff), enteroendocrine cells (stained for synaptophysin, arrows), and Paneth cells (stained for lysozyme). c An enlarged view of a small intestinal crypt depicting two different stem cell regions; a quiescent stem cell zone (+4 position), and an active stem cell zone (+1 to +4 positions) scattered between the Paneth cells. The +4 label-retaining cells (LRCs) are normally maintained in a quiescent state through direct interaction with and signals generated from the niche, such as pericryptal fibroblast/myofibroblasts and adjacent enteroendocrine cells within the +4 region. CBCs, continuously activated by signals generated from stromal cells at the crypt base, are responsible for most of the regenerative capacity of the intestine under homeostatic conditions. A gradient of BMP signaling, known to inhibit proliferation, is established along the crypt-villus axis, with relatively high activity throughout the villus and correspondingly less activity within the crypt. An opposite gradient of Wnt signaling, providing an important proliferative stimulus, is highest at the crypt base and decreases toward the crypt-villus junction. (A, reproduced with permission from Dr. Hans Clevers, Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences and the University Medical Center Utrecht, Utrecht, The Netherlands)