Fig. 1

The structure and homeostatic maintenance of the intestinal epithelium. A, The small intestine is enriched with enterocytes and contains the crypt and villus structures, while the large intestine is enriched with goblet cells and only has the crypt structures. The cell constitution of both small and large intestinal epithelia is driven by Lgr5 + intestinal stem cells (ISCs) at the bottom of the crypt. The fate of ISCs is regulated by niche factors from the surrounding stromal cells or the epithelium cells themselves, such as Paneth cells. Wnt and EGF signaling promote proliferation, and their activities are high in the crypt and decrease gradually towards the villus. In contrast, BMP signaling promotes differentiation, inhibits proliferation, and induces cell death, and its activity increases gradually towards the villus tip. B, The proliferation and differentiation trajectory of intestinal epithelium. ISCs undergo self-renewal and meanwhile generate transit-amplifying (TA) cells. TA cells are fast proliferating and produce enterocyte and secretory progenitors, which further differentiate into enterocytes and Paneth, goblet, enteroendocrine and tuft cells, respectively. Tuft cells have also been suggested to derive from enterocyte progenitors