Cigarette Smoke Specifically Affects Small Airway Epithelial Cell Populations and Triggers the Expansion of Inflammatory and Squamous Differentiation Associated Basal Cells

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2021
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Gindele, Julia A.
Kiechle, Tobias
Shen, Yang
Leparc, Germán G.
Stierstorfer, Birgit
Stahl, Heiko
Schymeinsky, Jürgen
Baum, Patrick
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Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and causes remodeling of the small airways. However, the exact smoke-induced effects on the different types of small airway epithelial cells (SAECs) are poorly understood. Here, using air-liquid interface (ALI) cultures, single-cell RNA-sequencing reveals previously unrecognized transcriptional heterogeneity within the small airway epithelium and cell type-specific effects upon acute and chronic cigarette smoke exposure. Smoke triggers detoxification and inflammatory responses and aberrantly activates and alters basal cell differentiation. This results in an increase of inflammatory basal-to-secretory cell intermediates and, particularly after chronic smoke exposure, a massive expansion of a rare inflammatory and squamous metaplasia associated KRT6A+ basal cell state and an altered secretory cell landscape. ALI cultures originating from healthy non-smokers and COPD smokers show similar responses to cigarette smoke exposure, although an increased pro-inflammatory profile is conserved in the latter. Taken together, the in vitro models provide high-resolution insights into the smoke-induced remodeling of the small airways resembling the pathological processes in COPD airways. The data may also help to better understand other lung diseases including COVID-19, as the data reflect the smoke-dependent variable induction of SARS-CoV-2 entry factors across SAEC populations.

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570 Biowissenschaften, Biologie
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single-cell transcriptomics; small airway epithelial cells; cigarette smoke; COPD; basal cells; lineage trajectory; ACE2
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ISO 690WOHNHAAS, Christian T., Julia A. GINDELE, Tobias KIECHLE, Yang SHEN, Germán G. LEPARC, Birgit STIERSTORFER, Heiko STAHL, Florian GANTNER, Jürgen SCHYMEINSKY, Patrick BAUM, 2021. Cigarette Smoke Specifically Affects Small Airway Epithelial Cell Populations and Triggers the Expansion of Inflammatory and Squamous Differentiation Associated Basal Cells. In: International Journal of Molecular Sciences (IJMS). MDPI. 2021, 22(14), 7646. eISSN 1422-0067. Available under: doi: 10.3390/ijms22147646
BibTex
@article{Wohnhaas2021-07-16Cigar-54516,
  year={2021},
  doi={10.3390/ijms22147646},
  title={Cigarette Smoke Specifically Affects Small Airway Epithelial Cell Populations and Triggers the Expansion of Inflammatory and Squamous Differentiation Associated Basal Cells},
  number={14},
  volume={22},
  journal={International Journal of Molecular Sciences (IJMS)},
  author={Wohnhaas, Christian T. and Gindele, Julia A. and Kiechle, Tobias and Shen, Yang and Leparc, Germán G. and Stierstorfer, Birgit and Stahl, Heiko and Gantner, Florian and Schymeinsky, Jürgen and Baum, Patrick},
  note={Article Number: 7646}
}
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