title: Uroplakin 3a+Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair.
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.
authors.affiliation: 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.
authors.forename: Arjun
authors.initials: A
authors.lastname: Guha
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India.
authors.forename: Aditya
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bengaluru 560065, India; SASTRA University, Thirumalaisamudram, Thanjavur, Tamil Nadu 613401, India.
authors.forename: Aradhya
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Biostatistics, Boston University, Boston, MA 02118, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Sebastiani
authors.affiliation: 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.
authors.forename: Wellington V
authors.initials: WV
authors.lastname: Cardoso
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D055745:Bronchioles / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D019070:Cell Lineage / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009281:Naphthalenes / Q000633:toxicity; D046568:Neuroepithelial Bodies / Q000378:metabolism / Q000473:pathology; D011650:Pulmonary Alveoli / Q000293:injuries; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D060171:Uroplakin III / Q000096:biosynthesis* / Q000235:genetics; D014945:Wound Healing
chemical_list: D009281:Naphthalenes; C554661:Upk3a protein, mouse; D060171:Uroplakin III; D001761:Bleomycin; C031721:naphthalene
keywords: Uroplakin 3a; airway repair; neuroepithelial bodies; variant club cells