GSE135188
Intermittent exposure to whole cigarette smoke alters the differentiation of primary small airway epithelial cells in the air-liquid interface culture
Cigarette smoke (CS) is the leading cause to develop COPD. Therefore, we investigated the pathologic effects of whole CS on the differentiation of primary small airway epithelial cells (SAEC), from three healthy donors and three COPD patients, cultured under ALI (air-liquid interface) conditions. The analysis of the epithelial physiology demonstrated that CS impaired barrier formation and reduced cilia beat activity. Although, COPD-derived ALI cultures preserved some features known from COPD patients, the CS-induced effects were similarly pronounced in ALI cultures from patients compared to healthy controls. A RNA sequencing analysis revealed the deregulation for marker genes for basal cells and secretory cells upon CS exposure. The comparison between gene signatures obtained from our in vitro model (CS vs. air) with a published data set from human epithelial brushes (smoker vs. non-smoker) reveals a high degree of similarity between the deregulated genes and pathways.  ALI culture has been generated utilising cells obtained from 3 COPD and 3 healthy subjects. Subsequently cultures have been treated with CS and air respectively for 33 days. Gene expression profiles were generated using next generation sequencing. Overall design: ALI culture mRNA profiles of COPD and healthy control subjects. Cells from 3 COPD and 3 healthy control donors have been split into 6 ALI cultures, each, resulting in overall 36 culture wells. Half of the wells per donor have been treated with CS and the other half with air. Expression data were generated using Illumina HiSeq3000.