TY - JOUR T1 - Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution JF - bioRxiv DO - 10.1101/484394 SP - 484394 AU - Grant E. Duclos AU - Vitor H. Teixeira AU - Patrick Autissier AU - Yaron B. Gesthalter AU - Marjan A. Reinders-Luinge AU - Robert Terrano AU - Yves M. Dumas AU - Gang Liu AU - Sarah A. Mazzilli AU - Corry-Anke Brandsma AU - Maarten van den Berge AU - Sam M. Janes AU - Wim Timens AU - Marc E. Lenburg AU - Avrum Spira AU - Joshua D. Campbell AU - Jennifer Beane Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/12/02/484394.abstract N2 - The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to perform functions, such as mucociliary clearance, that defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, the precise effects of this exposure on specific cell types are not well-understood. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses identified thirteen cell clusters defined by unique combinations of nineteen distinct gene sets. Expression of a set of toxin metabolism genes localized to ciliated cells from smokers. Smoking-induced airway remodeling was characterized by a loss of club cells and extensive goblet cell hyperplasia. Finally, we identified a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular and molecular alterations in the human bronchial epithelium that may contribute to the onset of smoking-associated lung diseases. ER -