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Updated: May 18, 2026

Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
Published on: July 27, 2022
Dll1+ secretory progenitor cells revert to stem cells upon crypt damage
Johan H van Es1, Toshiro Sato1, Marc van de Wetering1
1Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
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 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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