Butyrate consumption of differentiated colonocytes in the upper crypt promotes homeostatic proliferation of stem and progenitor cells near the crypt base

The mammalian intestinal tract epithelium is renewed every ~4–6 days, which is arguably the most rapidly turned over tissue in the body. Cellular turnover is facilitated by the intestinal epithelium being organized as crypts with highly proliferative stem cells and progenitor/transit-amplifying cells located near the crypt base and quiescent, terminally-differentiated cell types such as enterocytes, goblet cells, and enteroendocrine cells located above that undergo apoptosis and exfoliate into the lumen (Figure 1A). In recent years, tremendous progress has been made identifying Lgr5+ stem cells and crucial factors within the stem-cell niche such as Wnts, R-spondins, BMPs, Noggin, and the Notch pathway (1). This knowledge has been exploited to create 3D organoid culture systems that recapitulate the crypt with respect to stem cell renewal and their ability to give rise to descendants that represent each differentiated cell type.