Amplified aberrant small airway basal stem cells contribute to pathogenesis of bronchiectasis

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Bronchiectasis is a chronic obstructive airway disease characterized by airway dilation, mucus overproduction, chronic inflammation, and fibrosis. The role of airway basal stem cells (S-ABSCs) in its pathogenesis is not well understood. This study developed a novel feeder-free cloning technology to isolate and expand S-ABSCs from broncho-alveolar lavage fluids (BALFs) of patients with non-cystic fibrosis bronchiectasis (NCF-BEs) and non-chronic lung diseases (ND-Ctrs). In both ex-vivo and in-vivo models, S-ABSCs from NCF-BEs regenerated airway epithelia exhibiting bronchiectasis-like pathology, while those from ND-Ctrs formed normal small airways. Transcriptomic and single-cell RNA sequencing analyses revealed distinct gene expression patterns in NCF-BE-derived S-ABSCs related to mucus production, inflammation, and ECM remodeling. These cells also showed altered responses to respiratory microbes, potentially contributing to disease exacerbations. This work highlights the role of pathogenic S-ABSCs in chronic respiratory diseases and suggests them as potential therapeutic targets. erj;66/suppl_69/OA2314/F1 F1 F1 erj;66/suppl_69/OA2314/F2 F2 F2

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