Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair

Publication date: 11 April 2017
Source:Cell Reports, Volume 19, Issue 2
Author(s): Arjun Guha, Aditya Deshpande, Aradhya Jain, Paola Sebastiani, Wellington V. Cardoso
There is evidence that certain club cells (CCs) in the murine airways associated with neuroepithelial bodies (NEBs) and terminal bronchioles are resistant to the xenobiotic naphthalene (Nap) and repopulate the airways after Nap injury. The identity and significance of these progenitors (variant CCs, v-CCs) have remained elusive. A recent screen for CC markers identified rare Uroplakin3a (Upk3a)-expressing cells (U-CCs) with a v-CC-like distribution. Here, we employ lineage analysis in the uninjured and chemically injured lungs to investigate the role of U-CCs as epithelial progenitors. U-CCs proliferate and generate CCs and ciliated cells in uninjured airways long-term and, like v-CCs, after Nap. U-CCs have a higher propensity to generate ciliated cells than non-U-CCs. Although U-CCs do not contribute to alveolar maintenance long-term, they generate alveolar type I and type II cells after Bleomycin (Bleo)-induced alveolar injury. Finally, we report that Upk3a⁺ cells exist in the NEB microenvironment of the human lung and are aberrantly expanded in conditions associated with neuroendocrine hyperplasias.

Graphical abstract

Teaser

Guha et al. demonstrate, using lineage analysis, that Uroplakin 3a⁺ club cells (U-CCs) contribute toward airway maintenance and post-injury repair and generate both club and ciliated cells. These progenitors can also contribute to alveolar repair after bleomycin injury.


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