The multi-omics spatial lung atlas reveales new cell states and their functions in airway mesenchyme

The mesenchymal populations of the human airways often receive less attention compared to the parenchyma and airway surface epithelium and contribute to mucosal immunity via immune cell recruitment and entry. We collected deep tissue pieces from the human airways for transcriptional and spatial profiling to provide full characterisation of the mesenchymal populations including fibroblasts, muscle and vasculature. Within the fibroblast compartment we see 11 different populations, including peribronchial fibroblasts, and associate them with COPD. The single-nuclei RNA-seq enables the capture of a more diverse range of cells by removing dissociation biases, which allowed us to characterise the transcriptome of airway smooth muscle that we associate with the nerve synapse function important for bronchoconstriction. Finally, the studies in the vasculature compartment allow us to distinguish between systemic and pulmonary circulation, as well as enable the discovery of a novel immune-recruitment perivascular cell in the airways showing similarity to lymph node vasculature. Overall, we provide distinction of multiple novel cell types on the transcriptional level, and suggest their relevance in mucosal immunity and disease.