RT Journal Article SR Electronic T1 Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaaw3413 DO 10.1126/sciadv.aaw3413 VO 5 IS 12 A1 Duclos, Grant E. A1 Teixeira, Vitor H. A1 Autissier, Patrick A1 Gesthalter, Yaron B. A1 Reinders-Luinge, Marjan A. A1 Terrano, Robert A1 Dumas, Yves M. A1 Liu, Gang A1 Mazzilli, Sarah A. A1 Brandsma, Corry-Anke A1 van den Berge, Maarten A1 Janes, Sam M. A1 Timens, Wim A1 Lenburg, Marc E. A1 Spira, Avrum A1 Campbell, Joshua D. A1 Beane, Jennifer YR 2019 UL http://advances.sciencemag.org/content/5/12/eaaw3413.abstract AB The human bronchial epithelium is composed of multiple distinct cell types that cooperate to defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, its precise effects on specific cell types and overall tissue composition are unclear. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never and six current smokers. Unsupervised analyses led to the characterization of a set of toxin metabolism genes that localized to smoker ciliated cells, tissue remodeling associated with a loss of club cells and extensive goblet cell hyperplasia, and a previously unidentified peri-goblet epithelial subpopulation in smokers who expressed a marker of bronchial premalignant lesions. Our data demonstrate that smoke exposure drives a complex landscape of cellular alterations that may prime the human bronchial epithelium for disease.