Wnt control of stem cells and differentiation in the intestinal epithelium

The intestinal epithelium represents a very attractive experimental model for the study of integrated key cellular processes such as proliferation and differentiation. The tissue is subjected to a rapid and perpetual self-renewal along the crypt–villus axis. Renewal requires division of multipotent...

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Bibliographic Details
Published in:Experimental cell research 2005-06, Vol.306 (2), p.357-363
Main Authors: Pinto, Daniel, Clevers, Hans
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ADENOMAS
Animals
CARCINOGENESIS
Cell Differentiation
CELL PROLIFERATION
Colorectal cancer
Crypt–villus axis
EPITHELIUM
HOMEOSTASIS
Humans
Intercellular Signaling Peptides and Proteins - physiology
Intestinal epithelium
Intestinal Mucosa - cytology
Intestinal Mucosa - physiology
MICE
MUTATIONS
PHENOTYPE
Signal Transduction - physiology
STEM CELLS
Stem Cells - physiology
Wnt Proteins
Wnt/β-catenin signaling
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Summary:The intestinal epithelium represents a very attractive experimental model for the study of integrated key cellular processes such as proliferation and differentiation. The tissue is subjected to a rapid and perpetual self-renewal along the crypt–villus axis. Renewal requires division of multipotent stem cells, still to be morphologically identified and isolated, followed by transit amplification, and differentiation of daughter cells into specialized absorptive and secretory cells. Our understanding of the crucial role played by the Wnt/β-catenin signaling pathway in controlling the fine balance between cell proliferation and differentiation in the gut has been significantly enhanced in recent years. Mutations in some of its components irreversibly lead to carcinogenesis in humans and in mice. Here, we discuss recent advances related to the Wnt/β-catenin signaling pathway in regulating intestinal stem cells, homeostasis, and cancer. We emphasize how Wnt signaling is able to maintain a stem cell/progenitor phenotype in normal intestinal crypts, and to impose a very similar phenotype onto colorectal adenomas.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2005.02.022