A transcriptomic comparison between nasal and bronchial airway epithelia from children

Abstract

Introduction: The invasive nature of accessing bronchial epithelial cells limits the capacity to source and utilise these cells for research purposes. Nasal epithelial cells have been identified as a potential surrogate however, there is conflicting evidence to support this. Aim: To compare baseline transcriptomic differences between nasal and bronchial airway epithelial cells. Methods: Matched Nasal and Bronchial Epithelial cells (NEC and BEC respectively) were obtained via non-bronchoscopic brushings from 32 healthy children (mean age: 5.7 years, 15 males). Total RNA was extracted, sequenced via Illumina and differential gene expression analysis was performed (DESeq2 and Ingenuity Systems). Results: RNA-seq analysis identified 3,500 differentially expressed genes, where 2,388 genes were significantly upregulated, in NEC compared to BEC samples (±2-fold, adjusted p≤0.05). The most enriched pathways in NEC samples were related to; innate immune response (e.g. complement cascade; pattern recognition receptors, scavenger and Fcγ receptors), and metabolic processes (e.g. retinol metabolism, biological oxidations and cytochrome P450). Interestingly, NEC samples expressed genes related to innate immune pathways at lower levels compared to BEC, whereas genes related to metabolic pathways were expressed at significantly higher levels in NEC samples. Conclusions: This is the largest transcriptomic profiling study, to date, of ex vivo nasal and bronchial airway epithelial cells from a healthy paediatric cohort. Data generated here illustrates intrinsic differences between nasal and bronchial airway samples, however functional validation is necessary to confirm these observations.