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 Dll1 is expressed by a subset of immediate stem cell daughters. Lineage tracing in Dll1(GFP-ires-CreERT2) knock-in 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 Dll1(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.
Pubmed ID: 23000963 RIS Download
Animals | Cell Lineage | Cells, Cultured | Gene Knock-In Techniques | Intercellular Signaling Peptides and Proteins | Intestinal Mucosa | Mice | Organoids | Receptors, Notch | Stem Cells | Wnt3A Protein