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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, Eszter K. Vladar, Max A. Seibold
doi: https://doi.org/10.1101/612747
Katherine C. Goldfarbmuren
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Nathan D. Jackson
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Satria P. Sajuthi
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Nathan Dyjack
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Katie S. Li
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Cydney L. Rios
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Elizabeth G. Plender
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Michael T. Montgomery
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Jamie L. Everman
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
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Eszter K. Vladar
3Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado-AMC, Aurora, CO, 80045 USA
4Department of Cell and Developmental Biology, University of Colorado-AMC, Aurora, CO, 80045 USA
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Max A. Seibold
1Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, 80206 USA
2Department of Pediatrics, National Jewish Health, Denver, CO, 80206 USA
3Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado-AMC, Aurora, CO, 80045 USA
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  • For correspondence: seiboldm@njhealth.org
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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 nonsmokers, we generated a comprehensive atlas of epithelial cell types and states, connected these into lineages, and defined cell-specific responses to smoking. Our analysis inferred multi-state lineages that develop into surface mucus secretory and ciliated cells and contrasted these to the unique lineage and specialization of submucosal gland (SMG) cells. Our analysis also suggests a lineage relationship between tuft, pulmonary neuroendocrine, and the newly discovered CFTR-rich ionocyte cells. Our smoking analysis found 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 type-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.

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Posted April 17, 2019.
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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, Eszter K. Vladar, Max A. Seibold
bioRxiv 612747; doi: https://doi.org/10.1101/612747
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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, Eszter K. Vladar, Max A. Seibold
bioRxiv 612747; doi: https://doi.org/10.1101/612747

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