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TISSUE-SPECIFIC STEM CELLS

Conditional Stabilization of β-Catenin Expands the Pool of Lung Stem Cells

^aCenter for Lung Regeneration, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
^bDivision of Pulmonary Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston Massachusetts, USA;
^cDepartment of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Key Words. Adult stem cells • Progenitor cells • Regeneration • Bronchiole • Transgenic mouse

Correspondence: Barry R. Stripp, Ph.D.,2075 MSRBII, 106 Research Drive, DUMC Box 103000, Durham, North Carolina 27710, USA. Telephone: 919-668-7762; Fax: 919-684-5266; e-mail: barry.stripp{at}duke.edu

Received January 17, 2008; accepted for publication February 26, 2008.
First published online in STEM CELLS EXPRESS   March 20, 2008.



Maintenance of classic stem cell hierarchies is dependent upon stem cell self-renewal mediated in part by Wnt/β-catenin regulation of the cell cycle. This function is critical in rapidly renewing tissues due to the obligate role played by the tissue stem cell. However, the stem cell hierarchy responsible for maintenance of the conducting airway epithelium is distinct from classic stem cell hierarchies. The epithelium of conducting airways is maintained by transit-amplifying cells in the steady state; rare bronchiolar stem cells are activated to participate in epithelial repair only following depletion of transit-amplifying cells. Here, we investigate how signaling through β-catenin affects establishment and maintenance of the stem cell hierarchy within the slowly renewing epithelium of the lung. Conditional potentiation of β-catenin signaling in the embryonic lung results in amplification of airway stem cells through attenuated differentiation rather than augmented proliferation. Our data demonstrate that the differentiation-modulating activities of stabilized β-catenin account for expansion of tissue stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.

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