Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas

Science. 2012 Aug 10;337(6095):730-5. doi: 10.1126/science.1224676. Epub 2012 Aug 1.


The concept that tumors are maintained by dedicated stem cells, the so-called cancer stem cell hypothesis, has attracted great interest but remains controversial. Studying mouse models, we provide direct, functional evidence for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer. By "lineage retracing" using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the growth of established intestinal adenomas. These Lgr5(+) cells, which represent about 5 to 10% of the cells in the adenomas, generate additional Lgr5(+) cells as well as all other adenoma cell types. The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology*
  • Animals
  • Biomarkers / analysis
  • Cell Lineage
  • Cell Transformation, Neoplastic
  • Gene Expression Profiling
  • Gene Knock-In Techniques
  • Genes, Reporter
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Neoplasms / genetics
  • Intestinal Neoplasms / pathology*
  • Mice
  • Multipotent Stem Cells / pathology
  • Multipotent Stem Cells / physiology
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / physiology*
  • Paneth Cells / pathology
  • Receptors, G-Protein-Coupled / analysis*
  • Stem Cell Niche
  • Tamoxifen / pharmacology
  • Tumor Stem Cell Assay


  • Biomarkers
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Tamoxifen

Associated data

  • GEO/GSE37926