Whole-Exome Sequencing of Bronchial Epithelial Cells Reveals a Genetic Print of Airway Remodelling in COPD.
Adeline GermainJeanne-Marie PerotinGonzague DelepineMyriam PoletteGaëtan DesléeValérian DormoyPublished in: Biomedicines (2022)
The remodelling of the airways is a hallmark of chronic obstructive pulmonary disease, but it is highly heterogeneous and erratically distributed in the airways. To assess the genetic print of remodelling in chronic obstructive pulmonary disease (COPD), we performed a comparative whole-exome sequencing analysis on microdissected bronchial epithelia. Lung resections from four non-COPD and three COPD subjects (ex-smokers and current smokers) were formalin-fixed paraffin-embedded (FFPE). Non-remodelled and remodelled bronchial epithelia were isolated by laser microdissection. Genomic DNA was captured and sequenced. The comparative quantitative analysis identified a list of 109 genes as having variants in remodelled epithelia and 160 genes as having copy number alterations in remodelled epithelia, mainly in COPD patients. The functional analysis highlighted cilia-associated processes. Therefore, bronchial-remodelled epithelia appeared genetically more altered than non-remodelled epithelia. Characterizing the unique molecular print of airway remodelling in respiratory diseases may help uncover additional factors contributing to epithelial dysfunctions, ultimately providing additional targetable proteins to correct epithelial remodelling and improve lung function.
Keyphrases
- lung function
- copy number
- chronic obstructive pulmonary disease
- cystic fibrosis
- genome wide
- mitochondrial dna
- air pollution
- dna methylation
- newly diagnosed
- smoking cessation
- gene expression
- chronic kidney disease
- mass spectrometry
- high speed
- cell free
- circulating tumor
- circulating tumor cells
- genome wide analysis
- genome wide identification