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Originally published online as doi:10.2353/ajpath.2009.080758 on February 5, 2009

Published online before print February 5, 2009
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(American Journal of Pathology. 2009;174:715-721.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080758

Mini-Review

Wnt Signaling, Lgr5, and Stem Cells in the Intestine and Skin

Andrea Haegebarth and Hans Clevers

From the Hubrecht Institute- Royal Netherlands Academy of Arts and Sciences and the University Medical Center Utrecht, Utrecht, The Netherlands

Abstract

Stem cells hold great promise for regenerative medicine, but have remained elusive in many tissues because of a lack of adequate definitive markers. Progress in mouse genetics has provided the tools for characterization and validation of stem cell markers by functional and/or lineage tracing assays. The Wnt target gene Lgr5 has been recently identified as a novel stem cell marker of the intestinal epithelium and the hair follicle. In the intestine, Lgr5 is exclusively expressed in cycling crypt base columnar cells. Genetic lineage-tracing experiments revealed that crypt base columnar cells are capable of self-renewal and multipotency, thus representing genuine intestinal stem cells. In the stem cell niche of the murine hair follicle, Lgr5 is expressed in actively cycling cells. Transplantation and lineage tracing experiments have demonstrated that these Lgr5+ve cells maintain all cell lineages of the hair follicle throughout long periods of time and can build entire new hair follicles. Expression of Lgr5 in multiple other organs indicates that it may represent a global marker of adult stem cells. This review attempts to provide a comprehensive overview of the stem cell compartments in the intestine and skin with a focus on the cycling, yet long-lived and multipotent, Lgr5+ve stem cell populations.




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