Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung.
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.
McQualter
Jonathan L
JL
Australian Stem Cell Centre, Clayton, Victoria 3800, Australia. jonathan.mcqualter@stemcellcentre.edu.au
Yuen
Karen
K
Williams
Brenda
B
Bertoncello
Ivan
I
D000375:Aging; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D015703:Antigens, CD; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D017228:Hepatocyte Growth Factor