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Background
Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single‐cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single‐cell level.
Methods
We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL‐4 stimulation, and cell‐specific marker genes and proteins were identified.
Results
We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell‐specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+‐ciliated cells were sub‐classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL‐4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation.
Conclusion
The effects of IL‐4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell‐specific markers that might be pivotal for investigating respiratory inflammatory diseases.
This study investigates the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single‐cell level. The effects of IL‐4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. The trajectory analysis reveals deuterosomal cells as precursor cells of multiciliated cells. Common ciliated cell marker (FOXJ1), multiciliated cell marker (CCNO), and deuterosomal cell markers (CDC20 and CDK1) are reduced by IL‐4 treatment; IL‐13 shows similar inhibitory effect.Abbreviations: CCNO, cyclin O; CDC20, cell division cycle 20; CDK1, cyclin‐dependent kinase 1; CTRL, control; FOXJ1, forkhead box J1; IL, interleukin; RNAseq, RNA sequencing