Investigation into the lung vasculature transcriptional signature during asthma using spatial transcriptomic

Goal: Understanding the lung spatial landscape of complex respiratory disorders such as asthma is essential to define novel pathways for diagnosis and original therapeutical approaches. Spatial transcriptomics is an emerging method that has the potential to radically changed our view of human lung biology. My project is exploring how this technology can be used to better understand asthma physiopathology. Methods: Using endobronchial biopsies from children and adult patients with asthma, we explored the spatial lung transcriptional landscape using the Nanostring GeoMix platform. Results: We focused our analysis on vascular related pathways as we recently described significant vascular remodelling in preclinical models of allergic asthma (Joulia et al. bioRxiv 2023). In childhood asthma samples, gene pathways related to extracellular matrix reorganisation and immunoregulation were enriched in vessel rich regions suggesting remodelling occurs in the subepithelial vasculature. These changes were linked with an increased presence of immune cells notably mast cells and their associated proteases. The latter could have detrimental impact on the functions of immune cells such as innate lymphoid cells or eosinophils. Conclusion: My work has highlighted vascular changes potentially associated with damage of blood vessel integrity during asthma. In summary, the development of spatial transcriptomic tools will be critical in generating novel insight into the physiopathology of asthma across the life course. Funded by the British Heart Foundation and the Wellcome Trust.