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Sci Adv. 2019 Dec 11;5(12):eaaw3413. doi: 10.1126/sciadv.aaw3413. eCollection 2019 Dec.

Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution.

Author information

1
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
2
Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
3
Boston University Flow Cytometry Core Facility, Boston University School of Medicine, Boston, MA, USA.
4
Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA.
5
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
6
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, Netherlands.
7
Department of Thoracic Medicine, University College London Hospital, London, UK.
8
Johnson & Johnson Innovation, Cambridge, MA, USA.

Abstract

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.

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