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

作者:van Es, Johan H.; Sato, Toshiro; van de Wetering, Marc; Lyubimova, Anna; Nee, Annie Ng Yee; Gregorieff, Alex; Sasaki, Nobuo; Zeinstra, Laura; van den Born, Maaike; Korving, Jeroen; Martens, Anton C. M.; Barker, Nick; van Oudenaarden, Alexander; Clevers, Hans*
来源:Nature Cell Biology, 2012, 14(10): 1099-+.
DOI:10.1038/ncb2581

摘要

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.