The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single-cell resolution

0573066 - BTÚ 2024 RIV NL eng J - Journal Article
De Rooij, L. P. M. H. - Becker, L. M. - Teuwen, L.-A. - Boeckx, B. - Jansen, S. - Feys, S. - Verleden, S. - Liesenborghs, L. - Stalder, A.K. - Libbrecht, S. - Van Buyten, T. - Philips, G. - Subramanian, A. - Dumas, S. J. - Meta, E. - Borri, M. - Sokol, L. - Dendooven, A. - Truong, A. C. K. - Gunst, J. - Van Mol, P. - Haslbauer, J. D. - Rohlenová, Kateřina - Menter, T. - Boudewijns, R. - Geldhof, V. - Vinckier, S. - Amersfoort, J. - Wuyts, W. - Van Raemdonck, D. … Total 48 authors
The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single-cell resolution.
Cardiovascular Research. Roč. 119, č. 2 (2023), s. 520-535. ISSN 0008-6363. E-ISSN 1755-3245
Institutional support: RVO:86652036
Keywords : SARS-CoV-2 * covid-19 * ipf * Transcriptomics * Single-nucleus RNA-seq * Lung * Endothelial cells
OECD category: Cardiac and Cardiovascular systems
Impact factor: 10.9, year: 2022
Method of publishing: Open access
https://academic.oup.com/cardiovascres/article/119/2/520/6673943?login=true

Aims Severe acute respiratory syndrome coronavirus-2 infection causes COVID-19, which in severe cases evokes life-threatening acute respiratory distress syndrome (ARDS). Transcriptome signatures and the functional relevance of non-vascular cell types (e.g. immune and epithelial cells) in COVID-19 are becoming increasingly evident. However, despite its known contribution to vascular inflammation, recruitment/invasion of immune cells, vascular leakage, and perturbed haemostasis in the lungs of severe COVID-19 patients, an in-depth interrogation of the endothelial cell (EC) compartment in lethal COVID-19 is lacking. Moreover, progressive fibrotic lung disease represents one of the complications of COVID-19 pneumonia and ARDS. Analogous features between idiopathic pulmonary fibrosis (IPF) and COVID-19 suggest partial similarities in their pathophysiology, yet, a head-to-head comparison of pulmonary cell transcriptomes between both conditions has not been implemented to date. Methods and results We performed single-nucleus RNA-sequencing on frozen lungs from 7 deceased COVID-19 patients, 6 IPF explant lungs, and 12 controls. The vascular fraction, comprising 38 794 nuclei, could be subclustered into 14 distinct EC subtypes. Non-vascular cell types, comprising 137 746 nuclei, were subclustered and used for EC-interactome analyses. Pulmonary ECs of deceased COVID-19 patients showed an enrichment of genes involved in cellular stress, as well as signatures suggestive of dampened immunomodulation and impaired vessel wall integrity. In addition, increased abundance of a population of systemic capillary and venous ECs was identified in COVID-19 and IPF. COVID-19 systemic ECs closely resembled their IPF counterparts, and a set of 30 genes was found congruently enriched in systemic ECs across studies. Receptor-ligand interaction analysis of ECs with non-vascular cell types in the pulmonary micro-environment revealed numerous previously unknown interactions specifically enriched/depleted in COVID-19 and/or IPF. Conclusions This study uncovered novel insights into the abundance, expression patterns, and interactomes of EC subtypes in COVID-19 and IPF, relevant for future investigations into the progression and treatment of both lethal conditions.
Permanent Link: https://hdl.handle.net/11104/0346389