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Cell Rep. 2017 Apr 11;19(2):246-254. doi: 10.1016/j.celrep.2017.03.051.

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

Author information

1
Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India; Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: arjung@instem.res.in.
2
Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India.
3
Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India; SASTRA University, Thirumalaisamudram, Thanjavur, Tamil Nadu 613401, India.
4
Department of Biostatistics, Boston University, Boston, MA 02118, USA.
5
Columbia 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. Electronic address: wvc2104@cumc.columbia.edu.

Abstract

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.

KEYWORDS:

Uroplakin 3a; airway repair; neuroepithelial bodies; variant club cells

PMID:
28402849
DOI:
10.1016/j.celrep.2017.03.051
[Indexed for MEDLINE]
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