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

Nat Cell Biol. 2012 Oct;14(10):1099-1104. doi: 10.1038/ncb2581. Epub 2012 Sep 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cell Lineage
  • Cells, Cultured
  • Gene Knock-In Techniques
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intestinal Mucosa / metabolism*
  • Mice
  • Organoids / metabolism
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / metabolism
  • Stem Cells / metabolism*
  • Wnt3A Protein / pharmacology

Substances

  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Notch
  • Wnt3A Protein
  • Wnt3a protein, mouse