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van Es, Johan H; Sato, Toshiro; van de Wetering, Marc; Lyubimova, Anna; Yee Nee, Annie Ng; Gregorieff, Alex; Sasaki, Nobuo; Zeinstra, Laura; van den Born, Maaike; Korving, Jeroen; Martens, Anton C M; Barker, Nick; van Oudenaarden, Alexander; Clevers, Hans
Nature cell biology, 10/2012, Letnik: 14, Številka: 10Journal Article
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.
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