Dll1+ secretory progenitor cells revert to stem cells upon crypt damage
Nature cell biology, 2012•nature.com
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 Dll1high 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 Dll1high cells form long-lived organoids (mini-guts) …
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 Dll1high 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 Dll1high cells form long-lived organoids (mini-guts) …
Abstract
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 Dll1GFP–ires–CreERT2 knock-in mice reveals that single Dll1high 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 Dll1high cells form long-lived organoids (mini-guts) on brief Wnt3A exposure. When Dll1high 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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