Cultured alveolar basal cells display similar characteristics and functional properties to airway basal cells
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This article is not in any list yet, why not save it to one of your lists.Abstract
Rationale
Basal cells (BC) appear ectopically within the lung parenchyma of interstitial lung disease (ILD) patients, potentially through migration of airway BC or though trans-differentiation of resident alveolar epithelial type 2 (AT2) cells. The exact origin, role, and function of these ectopic alveolar BC remains poorly understood. By comparing ectopic alveolar to “classical” airway BC, we aimed to get a better understanding of the origin and characteristics of alveolar BC in ILD.
Methods
Alveolar and airway BC were isolated from transbronchial- and airway mucosal biopsies (MB) of the same ILD patients. BC were cultured on plastic under submerged conditions, on an air liquid interface (ALI), or in a 3D organoid model. Additionally, BC were intratracheally injected into bleomycin-challenged mice. Samples were analyzed by single cell RNA sequencing (scRNA-seq), TaqMan RT-PCR, immunocytochemistry/immunofluorescence (ICC/IF), or immunohistochemistry (IHC)/IF.
Results
scRNA-seq analysis revealed several differentially expressed genes in alveolar compared to airway BC, which, however, did not include specific AT2 cell marker genes. Expression of BC markers and the capacity for wound repair, proliferation, organoid formation and differentiation were not significantly different between cultured BC originating from the different locations. Furthermore, there was no difference in engraftment and differentiation potential after instillation into bleomycin-injured mice between the two human BC types.
Conclusion
Close similarities between alveolar and airway BC suggest that the specific pro-fibrotic microenvironment, rather than a cell intrinsic functional failure, determines alveolar BC characteristics and functions in ILD.
