Characteristics, similarities and differences comparing fibrotic alveolar to airway basal cells

Abstract

<b>Rationale:</b> In patients with interstitial lung diseases (ILD) basal cells accumulate within areas of pathological bronchiolization and honeycomb cysts in the peripheral lung. We have previously demonstrated the disease-enriched outgrowth of alveolar basal cells and an anti-fibrotic effect of their secretome in vitro and in vivo. Here, we aimed to characterize similarities and differences between fibrotic alveolar- and airway basal cells. <b>Methods:</b> Alveolar- and airway-derived basal cells were cultured from peripheral lung tissue obtained via transbronchial biopsies (TBB) and from proximal airway via mucosal biopsies (MB) in the same ILD patients. The cells were cultured in an epithelial cell specific growth medium (Cnt-PR-A) and analyzed by single cell RNA sequencing (scRNA-seq), proliferation- and scratch assays, and in an air-liquid-interface (ALI). <b>Results:</b> Both alveolar- and airway basal cells expressed canonical basal cell markers (TP63, KRT5, KRT14, KRT17), and showed similar capacities for wound repair, proliferation and differentiation into mucociliary epithelium. Interestingly, scRNA-seq analysis revealed clear transcriptomic differences between fibrotic alveolar- and airway-derived basal cells. <b>Conclusion:</b> The transcriptomic differences between alveolar basal cells and airway basal cells from lung of ILD patients might be due to the different microenvironment and will be useful to understand the role, function and origin of alveolar basal cells in ILD. Supported by a project grant (310030_192536) by the Swiss National Research Foundation.