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Disease-dependent airway epithelial responses to acute electronic cigarette aerosol exposure: a pilot single-cell analysis
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DOI：10.1093/toxsci/kfag068.png)
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Abstract
En 中文
Electronic cigarette (e-cig) use is increasingly common among individuals with asthma, yet the cell type-specific airway responses to e-cig exposure remain poorly understood. Because asthma is characterized by altered epithelial composition and heightened inflammatory susceptibility, e-cig exposure could elicit disease-dependent epithelial responses in asthmatic airways. Here, we used single-cell RNA sequencing to define responses to acute e-cig exposure in human primary airway epithelial cells differentiated at air-liquid interface from healthy and asthmatic donors. Cultures were exposed to e-cig aerosols for 30 min and analyzed 24 hrs later. Ten epithelial and stromal populations were identified. At baseline, asthma-derived cultures showed descriptive differences in cell-type composition compared with healthy-derived cultures, while acute e-cig exposure produced only modest additional changes in relative abundance. In contrast, transcriptional responses were disease dependent. Asthma-derived ATII, basal, goblet, mesenchymal, and mesothelial cells showed distinct inflammatory and immediate-early gene-expression changes, whereas healthy-derived cultures showed defense- and stress-associated responses. Pathway-level analysis showed enrichment of inflammatory signaling, injury/stress-response, and migration/ECM-related pathways in selected asthma-derived populations, while healthy-derived ATII and club cells were associated with defense and biotic-response pathways. SenMayo analysis showed cell type-specific patterns of senescence-associated gene set enrichment, with the strongest signal in club cells, together with increased CDKN2A and CDKN1A expression in asthma-derived epithelial populations. These findings suggest that asthma-associated epithelial states shape cell type-specific inflammatory, stress-associated, and senescence-related transcriptional responses to acute e-cig exposure.
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