Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair
Summary: 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 (var...
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doaj-fb39119202834e13916bce6664544d112020-11-24T21:34:06ZengElsevierCell Reports2211-12472017-04-01192246254Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury RepairArjun Guha0Aditya Deshpande1Aradhya Jain2Paola Sebastiani3Wellington V. Cardoso4Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India; Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA; Corresponding authorInstitute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, IndiaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India; SASTRA University, Thirumalaisamudram, Thanjavur, Tamil Nadu 613401, IndiaDepartment of Biostatistics, Boston University, Boston, MA 02118, USAColumbia Center for Human Development, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA; Corresponding authorSummary: 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. : 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. Keywords: variant club cells, neuroepithelial bodies, Uroplakin 3a, airway repairhttp://www.sciencedirect.com/science/article/pii/S2211124717303972 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arjun Guha Aditya Deshpande Aradhya Jain Paola Sebastiani Wellington V. Cardoso |
spellingShingle |
Arjun Guha Aditya Deshpande Aradhya Jain Paola Sebastiani Wellington V. Cardoso Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair Cell Reports |
author_facet |
Arjun Guha Aditya Deshpande Aradhya Jain Paola Sebastiani Wellington V. Cardoso |
author_sort |
Arjun Guha |
title |
Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair |
title_short |
Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair |
title_full |
Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair |
title_fullStr |
Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair |
title_full_unstemmed |
Uroplakin 3a+ Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair |
title_sort |
uroplakin 3a+ cells are a distinctive population of epithelial progenitors that contribute to airway maintenance and post-injury repair |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2017-04-01 |
description |
Summary: 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. : 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. Keywords: variant club cells, neuroepithelial bodies, Uroplakin 3a, airway repair |
url |
http://www.sciencedirect.com/science/article/pii/S2211124717303972 |
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