Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium

Katherine C. Goldfarbmuren, Nathan D. Jackson, Satria P. Sajuthi, Nathan Dyjack, Katie S. Li, Cydney L. Rios, Elizabeth G. Plender, Michael T. Montgomery, Jamie L. Everman, Preston E. Bratcher, Eszter K. Vladar and Max A. Seibold ()
Additional contact information
Katherine C. Goldfarbmuren: National Jewish Health
Nathan D. Jackson: National Jewish Health
Satria P. Sajuthi: National Jewish Health
Nathan Dyjack: National Jewish Health
Katie S. Li: National Jewish Health
Cydney L. Rios: National Jewish Health
Elizabeth G. Plender: National Jewish Health
Michael T. Montgomery: National Jewish Health
Jamie L. Everman: National Jewish Health
Preston E. Bratcher: National Jewish Health
Eszter K. Vladar: University of Colorado-AMC
Max A. Seibold: National Jewish Health

Nature Communications, 2020, vol. 11, issue 1, 1-21

Abstract: Abstract Cigarette smoke first interacts with the lung through the cellularly diverse airway epithelium and goes on to drive development of most chronic lung diseases. Here, through single cell RNA-sequencing analysis of the tracheal epithelium from smokers and non-smokers, we generate a comprehensive atlas of epithelial cell types and states, connect these into lineages, and define cell-specific responses to smoking. Our analysis infers multi-state lineages that develop into surface mucus secretory and ciliated cells and then contrasts these to the unique specification of submucosal gland (SMG) cells. Accompanying knockout studies reveal that tuft-like cells are the likely progenitor of both pulmonary neuroendocrine cells and CFTR-rich ionocytes. Our smoking analysis finds that all cell types, including protected stem and SMG populations, are affected by smoking through both pan-epithelial smoking response networks and hundreds of cell-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.

Date: 2020
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DOI: 10.1038/s41467-020-16239-z

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