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The manuscript "Integrated single-cell RNA sequencing analysis reveals alterations of ageing human lung endothelium heterogeneity in idiopathic pulmonary fibrosis" has been uploaded to MedRxiv. The work focuses on characterising the transcriptional heterogeneity of the ageing endothelium in idiopathic pulmonary fibrosis.
Increasing age is the main risk factor for chronic lung diseases (CLD) including idiopathic pulmonary fibrosis (IPF). Halting or reversing progression of IPF remains an unmet clinical need due to limited knowledge of underlying mechanisms. In particular, the contribution of the endothelium to ageing in human lung under physiological conditions and in IPF remains insufficiently understood. Our findings reveal a previously unrecognised phenomenon of ageing human lung endothelium re-programming towards an “IPF endothelium” state, suggesting potential avenues for therapeutic management or biomarker discovery for diagnostics or prognostics of IPF. Our study creates a conceptual framework for appreciating the heterogeneity of ageing endothelium and its alterations in CLDs and diseases associated with fibrosis in other organs, including lymphoedema and cancer.
Spatial relationships between ageing human blood endothelial subpopulations in the IPF lung. 3D pseudo time lineage analysis showing spatial relationships between subpopulations of ageing human BEC within a 3D UMAP. BEC - Blood endothelial cells, UMAP - Uniform manifold approximation projection.