secretory progenitor cells revert to stem cells upon crypt damage

[Lgr5.sup.+] intestinal stem cells generate enterocytes and secretory cells. Secretory lineage commitment requires Notch silencing. The Notch ligand Dll1 is expressed by a subset of immediate stem cell daughters. Lineage tracing in [Dll1.sup.GFP-ires-CretERT2] knock-in mice reveals that single [Dll1.sup.high] cells generate small, short-lived clones containing all four secretory cell types. Lineage specification thus occurs in immediate stem cell daughters through Notch lateral inhibition. Cultured [Dll1.sup.high] cells form long-lived organoids (mini-guts) on brief Wnt3A exposure. When [Dll1.sup.high] cells are genetically marked before tissue damage, stem cell tracing events occur. Thus, secretory progenitors exhibit plasticity by regaining stemness on damage.