Cell, 2012-03, Vol.149 (1), p.146-158
2012
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Details
- Autor(en) / Beteiligte
- Titel
- The Pan-ErbB Negative Regulator Lrig1 Is an Intestinal Stem Cell Marker that Functions as a Tumor Suppressor
- Ist Teil von
- Cell, 2012-03, Vol.149 (1), p.146-158
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- 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. [Display omitted] ► Lrig1, an ErbB negative regulator, marks quiescent intestinal stem cells ► Lrig1 and Lgr5 transcriptome profiles are distinct ► Loss of APC in Lrig1+ cells results in intestinal adenomas ► Functionally null Lrig1 mice develop duodenal adenomas Loss of calibrated EGFR/ErbB signaling in quiescent intestinal stem cells has neoplastic consequences, generating advanced colon adenomas. Although Lrig1+ cells are distinct from proliferating Lgr5+ cells, they are located at the base of the crypt.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0092-8674eISSN: 1097-4172DOI: 10.1016/j.cell.2012.02.042Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3563328
- Format
- –
- Schlagworte
- Adenoma, Adenoma - pathology, adenomatous polyposis coli, Adenomatous Polyposis Coli Protein - metabolism, Animals, Cell cycle, cells, Colon - cytology, Colon - metabolism, ErbB protein, Gene expression, Gene Expression Profiling, gene expression regulation, Gene mapping, genes, Genes, Tumor Suppressor, Humans, Injuries, Intestinal Neoplasms - pathology, Intestine, Intestine, Small - cytology, Intestine, Small - metabolism, Membrane Glycoproteins - metabolism, Mice, Neoplasia, neoplasms, Nerve Tissue Proteins - metabolism, Receptor, Epidermal Growth Factor - metabolism, Receptors, G-Protein-Coupled - metabolism, Signal Transduction, Stem cells, Stem Cells - cytology, Stem Cells - metabolism, transcriptomics, Tumor suppressor genes