Cell-intrinsic differences between human airway epithelial cells from children and adults

Maughan, Elizabeth F.; Nigro, Ersilia; Pennycuick, Adam; Gowers, Kate H.C.; Denais, Celine; Gómez-López, Sandra; Lazarus, Kyren A.; Butler, Colin R.; Lee, Dani Do Hyang; Orr, Jessica C.; Teixeira, Vitor H.; Hartley, Benjamin E.; Hewitt, Richard J.; Yaghchi, Chadwan Al; Sandhu, Gurpreet S.; Birchall, Martin A.; O’Callaghan, Christopher; Smith, Claire M.; De Coppi, Paolo; Hynds, Robert E.; Janes, Sam M.

The airway epithelium is a key protective barrier whose integrity is preserved by the self-renewal and differentiation of basal progenitor cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic diseases, increasing age is a principle risk factor. In acute diseases, such as COVID-19, children suffer less severe symptoms than adults and have a lower rate of mortality. Few studies have explored differences between airway epithelial cells in children and adults to explain this age dependent variation in diseases. Here, we perform bulk RNA sequencing studies in laser-capture microdissected whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We find that, while the cellular composition of the paediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, paediatric airway epithelial cells displayed higher colony forming ability, better in vitro growth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences in airway epithelial gene expression between samples from children and adults. However, genes known to be associated with SARS-CoV-2 infection were not differentially expressed between children and adults. Our results chart cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults.