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

儿童和成人呼吸道上皮细胞的细胞内在差异

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作者: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

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.

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