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Evidence of an Epithelial Stem/Progenitor Cell Hierarchy in the Adult Mouse Lung

Jonathan L. McQualter, Karen Yuen, Brenda Williams and Ivan Bertoncello
Proceedings of the National Academy of Sciences of the United States of America
Vol. 107, No. 4 (Jan. 26, 2010), pp. 1414-1419
Stable URL: http://www.jstor.org/stable/40536342
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Evidence of an Epithelial Stem/Progenitor Cell Hierarchy in the Adult Mouse Lung
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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 colonyforming potential in vitro. We describe a population of $E_p CAM^{bl} \,CD49f^{pos} \,CD24^{low} $ epithelial cfus that generate colonies comprising airway, alveolar, or mixed lung epithelial cell lineages when cocultured with $E_p CAM^{neg} \,Cca - 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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