title: Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas.
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.
authors.affiliation: Hubrecht Institute, Koninklijke Nederlandse Akademie van Wetenschappen, and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.
authors.forename: Arnout G
authors.initials: AG
authors.lastname: Schepers
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Snippert
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Stange
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Born
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D055879:Gene Knock-In Techniques; D017930:Genes, Reporter; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D039902:Multipotent Stem Cells / Q000473:pathology / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000502:physiology*; D019879:Paneth Cells / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000032:analysis*; D055153:Stem Cell Niche; D013629:Tamoxifen / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
chemical_list: D015415:Biomarkers; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D013629:Tamoxifen