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The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor.

Cell | Mar 30, 2012

Lineage mapping has identified both proliferative and quiescent intestinal stem cells, but the molecular circuitry controlling stem cell quiescence is incompletely understood. By lineage mapping, we show Lrig1, a pan-ErbB inhibitor, marks predominately noncycling, long-lived stem cells that are located at the crypt base and that, upon injury, proliferate and divide to replenish damaged crypts. Transcriptome profiling of Lrig1(+) colonic stem cells differs markedly from the profiling of highly proliferative, Lgr5(+) colonic stem cells; genes upregulated in the Lrig1(+) population include those involved in cell cycle repression and response to oxidative damage. Loss of Apc in Lrig1(+) cells leads to intestinal adenomas, and genetic ablation of Lrig1 results in heightened ErbB1-3 expression and duodenal adenomas. These results shed light on the relationship between proliferative and quiescent intestinal stem cells and support a model in which intestinal stem cell quiescence is maintained by calibrated ErbB signaling with loss of a negative regulator predisposing to neoplasia.

Pubmed ID: 22464327 RIS Download

Mesh terms: Adenoma | Adenomatous Polyposis Coli Protein | Animals | Colon | Gene Expression Profiling | Genes, Tumor Suppressor | Humans | Intestinal Neoplasms | Intestine, Small | Membrane Glycoproteins | Mice | Nerve Tissue Proteins | Receptor, Epidermal Growth Factor | Receptors, G-Protein-Coupled | Signal Transduction | Stem Cells

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Associated grants

  • Agency: NCI NIH HHS, Id: CA46413
  • Agency: NCI NIH HHS, Id: P50CA095103
  • Agency: NCI NIH HHS, Id: P50 CA095103
  • Agency: NCI NIH HHS, Id: R01 CA046413
  • Agency: NIDDK NIH HHS, Id: P30 DK043351
  • Agency: NIGMS NIH HHS, Id: T32GM008554
  • Agency: NCI NIH HHS, Id: T32 CA119925
  • Agency: NIDDK NIH HHS, Id: P30 DK058404
  • Agency: NCI NIH HHS, Id: T32CA119925
  • Agency: NIDDK NIH HHS, Id: P30 DK078392
  • Agency: NCI NIH HHS, Id: CA151566
  • Agency: NCI NIH HHS, Id: R01 CA151566
  • Agency: NCI NIH HHS, Id: U01 CA084239
  • Agency: NCI NIH HHS, Id: U01CA084239
  • Agency: NIGMS NIH HHS, Id: T32 GM008554
  • Agency: NCATS NIH HHS, Id: UL1 TR000077

Mouse Genome Informatics (Data, Gene Annotation)

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