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

J.H. van Es, T. Sato, M. van de Wetering, A. Lyubimova, A.N. Nee, A. Gregorieff, N. Sasaki, L. Zeinstra, M. van den Born, J. Korving, A.C. Martens, N. Barker, A. van Oudenaarden, H. Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

543 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)1099-1104
JournalNature Cell Biology
Issue number10
Publication statusPublished - 2012


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