Abstract
BACKGROUND: Asthma exacerbation significantly contribute to disease mortality and result in heightened health care expenditures. This study was aimed at gaining important new insights into the heterogeneity of epithelial and immune cells and elucidating key regulatory genes involved in the pathogenesis of asthma exacerbation. METHODS: Functional enrichment, pseudotime, metabolism and cell-cell communication analyses of epithelial cells and immune cells in single-cell RNA sequencing (scRNA-seq) dataset were applied. Immune infiltration analysis was performed in bulk RNA sequencing (bulk RNA-seq) dataset. Key regulatory genes were obtained by taking the intersection of the differentially expressed genes (DEGs) between control and asthma group in epithelial cells, immune cells and bulk RNA-seq data. Asthma animal and in vitro cell line models were established to verify the key regulatory genes expression by employing quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: ScRNA-seq analysis identified 7 epithelial subpopulations and 14 distinct immune cell types based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of functional variations, dynamics, communication patterns and metabolic changes. Notably, TMPRSS11A, TUBA1A, SCEL, ICAM4, TMPRSS11B, IGFBP2, CLC, NFAM1 and F13A1 were identified as key regulatory genes of asthma. The results of the qRT-PCR demonstrated that the 9 key regulatory genes were involved in asthma. CONCLUSIONS: We systematically explored epithelial and immune characteristics in asthma exacerbation and identified 9 key regulatory genes underlying asthma occurrence and progression, which may be valuable for providing new insights into the cellular and molecular mechanisms driving asthma exacerbations.