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

Arnout G. Schepers, Hugo J. Snippert, Daniel E. Stange, Maaike Van Den Born, Johan H. Van Es, Marc Van De Wetering, Hans Clevers

Research output: Contribution to journalArticlepeer-review

835 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)730-735
Number of pages6
Issue number6095
Publication statusPublished - 10 Aug 2012
Externally publishedYes


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