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

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.

Pubmed ID: 23000963


  • van Es JH
  • Sato T
  • van de Wetering M
  • Lyubimova A
  • Nee AN
  • Gregorieff A
  • Sasaki N
  • Zeinstra L
  • van den Born M
  • Korving J
  • Martens AC
  • Barker N
  • van Oudenaarden A
  • Clevers H


Nature cell biology

Publication Data

October 3, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: U54 CA143874
  • Agency: NCI NIH HHS, Id: U54CA143874

Mesh Terms

  • Animals
  • Cell Lineage
  • Cells, Cultured
  • Gene Knock-In Techniques
  • Intercellular Signaling Peptides and Proteins
  • Intestinal Mucosa
  • Mice
  • Organoids
  • Receptors, Notch
  • Stem Cells
  • Wnt3A Protein