The pan-ErbB negative regulator lrig1 is an intestinal stem cell marker that functions as a tumor suppressor

Anne E. Powell, Yang Wang, Yina Li, Emily J. Poulin, Anna L. Means, Mary K. Washington, James N. Higginbotham, Alwin Juchheim, Nripesh Prasad, Shawn E. Levy, Yan Guo, Yu Shyr, Bruce J. Aronow, Kevin M. Haigis, Jeffrey L. Franklin, Robert J. Coffey

Research output: Contribution to journalArticlepeer-review

410 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)146-158
Number of pages13
JournalCell
Volume149
Issue number1
DOIs
Publication statusPublished - 2012 Mar 30

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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