Stem cells are dispensable for lung homeostasis but restore airways after injury

Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contributions of progenitor (Clara) and bronchiol...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-06, Vol.106 (23), p.9286-9291
Main Authors: Giangreco, Adam, Arwert, Esther N, Rosewell, Ian R, Snyder, Joshua, Watt, Fiona M, Stripp, Barry R
Format: Article
Language:English
Subjects:
Airway management
Animals
Beta cells
Biological Sciences
Bronchioles
Bronchioles - cytology
Cell lines
Chimerism
Cloning
DNA repair
Epithelial cells
Epithelial Cells - cytology
Female
Homeostasis
Lung - cytology
Lung - physiology
Lung diseases
Lungs
Male
Mice
Neural stem cells
Progenitor cells
Stem cells
Stem Cells - cytology
Stem Cells - physiology
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Summary:Local tissue stem cells have been described in airways of the lung but their contribution to normal epithelial maintenance is currently unknown. We therefore developed aggregation chimera mice and a whole-lung imaging method to determine the relative contributions of progenitor (Clara) and bronchiolar stem cells to epithelial maintenance and repair. In normal and moderately injured airways chimeric patches were small in size and not associated with previously described stem cell niches. This finding suggested that single, randomly distributed progenitor cells maintain normal epithelial homeostasis. In contrast we found that repair following severe lung injury resulted in the generation of rare, large clonal cell patches that were associated with stem cell niches. This study provides evidence that epithelial stem cells are dispensable for normal airway homeostasis. We also demonstrate that stem cell activation and robust clonal cellular expansion occur only during repair from severe lung injury.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0900668106