Cigarette Smoke Specifically Affects Small Airway Epithelial Cell Populations and Triggers the Expansion of Inflammatory and Squamous Differentiation Associated Basal Cells
| Autor: | Coralie Viollet, Florian Gantner, Patrick Baum, German Leparc, Heiko Stahl, Julia A. Gindele, Tobias Kiechle, Yang Shen, J. Schymeinsky, Christian T. Wohnhaas, Birgit Stierstorfer |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
basal cells small airway epithelial cells Cellular differentiation Squamous Differentiation Cell ACE2 Basal (phylogenetics) Pulmonary Disease Chronic Obstructive 0302 clinical medicine Smoke Biology (General) Spectroscopy Cells Cultured COPD cigarette smoke Smoking Cell Differentiation General Medicine Squamous metaplasia Computer Science Applications Chemistry medicine.anatomical_structure Airway Remodeling QH301-705.5 Primary Cell Culture Respiratory Mucosa lineage trajectory Catalysis Article Cigarette Smoking Inorganic Chemistry 03 medical and health sciences ddc:570 medicine Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 Neoplasms Basal Cell Lung business.industry Organic Chemistry Epithelial Cells medicine.disease respiratory tract diseases 030104 developmental biology 030228 respiratory system single-cell transcriptomics Alveolar Epithelial Cells Immunology Respiratory epithelium business |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 7646, p 7646 (2021) International Journal of Molecular Sciences Volume 22 Issue 14 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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