Figure 1.

(A) The intestinal epithelium is structurally organized into crypt-villus units. Stem cells and transit-amplifying cells in the crypt proliferate continuously to renew mature cells in the villi. In the crypt, Lgr5⁺ ISCs, CBCs, are intermingled with Paneth cells, differentiated and secretory cells that provide CBCs with growth signals. (B) Paneth cells are highly glycolytic. CBCs have more mitochondria than Paneth cells and have an oxidative metabolic profile. The lactate generated through glycolysis in Paneth cells is excreted and used by CBCs to drive oxidative metabolism, which supports their proliferation and differentiation. CBCs are dependent on oxidative metabolism as indicated by their sensitivity to inhibitors of oxidative phosphorylation (OXPHOS). In the schematic, orange indicates differentiated cells in villi, grey indicates transit-amplifying progenitor cells, green indicates CBCs, and brown indicates Paneth cells.