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

Maughan, E. F.; Nigro, E.; Pennycuick, A.; Gowers, K. H. C.; Denais, C.; Gomez-Lopez, S.; Lazarus, K. A.; Butler, C. R.; Lee, D. D. H.; Orr, J. C.; Teixeira, V. H.; Hartley, B. E.; Hewitt, R. J.; Al Yaghchi, C.; Sandhu, G. S.; Birchall, M. A.; O'Callaghan, C.; Smith, C. M.; De Coppi, P.; Hynds, R. E.; Janes, S. M.

doi:10.1101/2020.04.20.027144

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bioRxiv · 10.1101/2020.04.20.027144

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

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Abstract

The airway epithelium is a key protective barrier, the integrity of which is preserved by the self-renewal and differentiation of basal stem cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic lung diseases, increasing age is a principle risk factor. Few studies have explored the differences between airway epithelial cells in children and adults and how the function of basal stem cells changes during ageing is poorly understood. Here, we analyze airway epithelial cells from children and adults in homeostatic conditions (laser capture-microdissected whole epithelium and fluorescence-activated cell-sorted basal cells) and in proliferation-inducing cell culture conditions. We find that, while the cellular composition of the pediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, pediatric airway epithelial cells displayed higher colony-forming ability, sustained in vitro growth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences between epithelium from children and adults, including higher baseline interferon-associated gene expression in pediatric epithelium. Our results demonstrate cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/027144v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@b7a680org.highwire.dtl.DTLVardef@1145543org.highwire.dtl.DTLVardef@1e9a86aorg.highwire.dtl.DTLVardef@12fe0bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Maughan, E. F., Nigro, E., Pennycuick, A., Gowers, K. H. C., Denais, C., Gomez-Lopez, S., Lazarus, K. A., Butler, C. R., Lee, D. D. H., Orr, J. C., Teixeira, V. H., Hartley, B. E., Hewitt, R. J., Al Yaghchi, C., Sandhu, G. S., Birchall, M. A., O'Callaghan, C., Smith, C. M., De Coppi, P., Hynds, R. E., Janes, S. M.. 2020-04-20. Cell-intrinsic differences between human airway epithelial cells from children and adults. https://doi.org/10.1101/2020.04.20.027144

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