Lineage Tracing Reveals Lgr5<SUP>+</SUP> Stem Cell Activity in Mouse Intestinal Adenomas

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Arnout G. Schepers - (Author)
  • Hugo J. Snippert - (Author)
  • Daniel E. Stange - , Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden (Author)
  • Maaike van den Born - (Author)
  • Johan H. van Es - (Author)
  • Marc van de Wetering - (Author)
  • Hans Clevers - , Royal Netherlands Academy of Arts and Sciences (Author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)730-735
Number of pages6
JournalScience
Volume337
Issue number6095
Publication statusPublished - 10 Aug 2012
Peer-reviewedYes

External IDs

PubMed 22855427
Scopus 84864854371

Keywords

Keywords

  • Colorectal-cancer, Human colon, Differentiation, Identification, Origin, Tumors, Gene, Mice