Abstract
The role of lung epithelial stem cells in maintenance and repair of the adult lung is ill-defined, and their identity remains contentious because of the lack of definitive markers for their prospective isolation and the absence of clonogenic assays able to measure their stem/progenitor cell potential. In this study, we show that replication of epithelial–mesenchymal interactions in a previously undescribed matrigel-based clonogenic assay enables the identification of lung epithelial stem/progenitor cells by their colony-forming potential in vitro. We describe a population of EpCAM hi CD49f pos CD104 pos CD24 low epithelial cfus that generate colonies comprising airway, alveolar, or mixed lung epithelial cell lineages when cocultured with EpCAM neg Sca-1 pos lung mesenchymal cells. We show that soluble fibroblast growth factor-10 and hepatocyte growth factor partially replace the requirement for mesenchymal support of epithelial colony formation, allowing clonal passaging and demonstration of their capacity for self-renewal. These data support a model in which the adult mouse lung contains a minor population of multipotent epithelial stem/progenitor cells with the capacity for self-renewal and whose descendants give rise to airway and alveolar epithelial cell lineages in vitro.
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Dates
Type | When |
---|---|
Created | 15 years, 7 months ago (Jan. 4, 2010, 9:36 p.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 6:50 p.m.) |
Indexed | 1 day, 18 hours ago (Aug. 27, 2025, 11:45 a.m.) |
Issued | 15 years, 7 months ago (Jan. 4, 2010) |
Published | 15 years, 7 months ago (Jan. 4, 2010) |
Published Online | 15 years, 7 months ago (Jan. 4, 2010) |
Published Print | 15 years, 7 months ago (Jan. 26, 2010) |
@article{McQualter_2010, title={Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung}, volume={107}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0909207107}, DOI={10.1073/pnas.0909207107}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={McQualter, Jonathan L. and Yuen, Karen and Williams, Brenda and Bertoncello, Ivan}, year={2010}, month=jan, pages={1414–1419} }