Fig. 1

Current models of intestinal epithelium during homeostasis and regeneration. a During homeostasis, multipotent Lgr5⁺ ISCs maintain regular epithelial renewal. The base-locate Lgr5⁺ ISCs generate rapidly proliferating TA cells and further differentiated into the various cell lineages. b Tissue injury that results in the loss of Lgr5⁺ ISCs drives a regenerative response to recover the Lgr5⁺ ISC pool. Left: the reserve stem cell model: damage-resistant + 4 quiescent stem cells function as the “reserve stem cells” to refill the Lgr5⁺ pool and restore the epithelial architecture. Right: the dedifferentiation model: acute damages result in the loss of the Lgr5⁺ cells and trigger dedifferentiation of progenitors and mature cells to replenish the Lgr5⁺ ISC population