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

Elizabeth F Maughan; Robert E Hynds; Adam Pennycuick; Ersilia Nigro; Kate H C Gowers; Celine Denais; Sandra Gómez-López; Kyren A Lazarus; Jessica C Orr; David R Pearce; Sarah E Clarke; Dani Do Hyang Lee; Maximillian N J Woodall; Tereza Masonou; Katie-Marie Case; Vitor H Teixeira; Benjamin E Hartley; Richard J Hewitt; Chadwan Al Yaghchi; Gurpreet S Sandhu; Martin A Birchall; Christopher O'Callaghan; Claire M Smith; Paolo De Coppi; Colin R Butler; Sam M Janes

doi:10.1016/j.isci.2022.105409

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

iScience. 2022 Oct 20;25(11):105409. doi: 10.1016/j.isci.2022.105409. eCollection 2022 Nov 18.

Authors

Elizabeth F Maughan^{1

2}, Robert E Hynds², Adam Pennycuick¹, Ersilia Nigro¹, Kate H C Gowers¹, Celine Denais¹, Sandra Gómez-López¹, Kyren A Lazarus¹, Jessica C Orr¹, David R Pearce³, Sarah E Clarke¹, Dani Do Hyang Lee⁴, Maximillian N J Woodall⁴, Tereza Masonou⁴, Katie-Marie Case⁴, Vitor H Teixeira¹, Benjamin E Hartley⁵, Richard J Hewitt⁵, Chadwan Al Yaghchi⁶, Gurpreet S Sandhu⁶, Martin A Birchall⁷, Christopher O'Callaghan⁴, Claire M Smith⁴, Paolo De Coppi⁸, Colin R Butler^{2

5}, Sam M Janes¹

Affiliations

¹ Lungs for Living Research Centre, UCL Respiratory, University College London, London WC1E 6JF, UK.
² Epithelial Cell Biology in ENT Research (EpiCENTR) Group, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1DZ, UK.
³ University College London Cancer Institute, University College London, London WC1E 6DD, UK.
⁴ Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, University College London, London WC1E 1EH, UK.
⁵ Tracheal Service, Great Ormond Street Hospital, London WC1N 3JH, UK.
⁶ The National Centre for Airway Reconstruction, Department of Otolaryngology, Charing Cross Hospital, London W6 8RF, UK.
⁷ University College London Ear Institute, University College London, London WC1X 8EE, UK.
⁸ Stem Cell and Regenerative Medicine Section, University College London Great Ormond Street Institute of Child Health, University College London, London WC1N 1DZ, UK.

Abstract

The airway epithelium is a protective barrier that is maintained by the self-renewal and differentiation of basal stem cells. Increasing age is a principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in the airway epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites from pediatric and adult donors and compared their cellular composition and gene expression profile (in laser capture-microdissected whole epithelium, fluorescence-activated cell-sorted basal cells, and basal cells in cell culture). Histologically, pediatric and adult tracheobronchial epithelium was similar in composition. We observed age-associated changes in RNA sequencing studies, including higher interferon-associated gene expression in pediatric epithelium. In cell culture, pediatric cells had higher colony formation ability, sustained in vitro growth, and outcompeted adult cells in a direct competitive proliferation assay. Our results demonstrate cell-intrinsic differences between airway epithelial cells from children and adults in both homeostatic and proliferative states.

Keywords: Medical science; Molecular biology; Pediatrics.

Abstract

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