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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bronchi / drug effects*
  • Bronchi / metabolism
  • Epithelium / drug effects
  • Epithelium / pathology
  • Genetic Heterogeneity / drug effects
  • Goblet Cells / drug effects
  • Goblet Cells / pathology
  • Humans
  • Hyperplasia / chemically induced
  • Hyperplasia / genetics
  • Hyperplasia / pathology
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / pathology
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Smoking / adverse effects*
  • Transcription, Genetic / drug effects*
  • Transcription, Genetic / genetics