Dll1+ secretory progenitor cells revert to stem cells upon crypt damage

Lgr5(+) intestinal stem cells generate enterocytes and secretory cells. Secretory lineage commitment requires Notch silencing. The Notch ligand Dill is expressed by a subset of immediate stem cell daughters. Lineage tracing in Dll1(GFP-ires-CreERT2) mice reveals that single Dll1(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 Dll(1)high cells form long-lived organoids (mini-guts) on brief Wnt3A exposure. When Dll1(high) cells are genetically marked before tissue damage, stem cell tracing events occur. Thus, secretory progenitors exhibit plasticity by regaining stemness on damage.