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Mayr, C. ; Simon, L. ; Leuschner, G. ; Ansari, M. ; Schniering, J. ; Geyer, P.E.* ; Angelidis, I. ; Strunz, M. ; Singh, P. ; Kneidinger, N. ; Reichenberger, F. ; Silbernagel, E. ; Böhm, S.* ; Adler, H. ; Lindner, M. ; Maurer, B.* ; Hilgendorff, A. ; Prasse, A.* ; Behr, J. ; Mann, M.* ; Eickelberg, O.* ; Theis, F.J. ; Schiller, H. B.

Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers.

EMBO Mol. Med. 13:e12871 (2021)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulatory factor CFHR1. We further discovered CRTAC1 as a biomarker of alveolar type-2 epithelial cell health status in lavage fluid and plasma. Using cross-modal analysis and machine learning, we identified the cellular source of biomarkers and demonstrated that information transfer between modalities correctly predicts disease status, suggesting feasibility of clinical cell state monitoring through longitudinal sampling of body fluid proteomes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Biomarker ; Data Integration ; Fibrosis ; Proteomics ; Single-cell Rna-seq
ISSN (print) / ISBN 1757-4676
e-ISSN 1757-4684
Journal EMBO Molecular Medicine
Quellenangaben Volume: 13, Issue: 4, Pages: , Article Number: e12871 Supplement: ,
Publisher Wiley
Publishing Place Chichester
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
Research Unit Lung Repair and Regeneration (LRR)
Grants Bundesministerium fur Bildung und Forschung (BMBF)
Max-Planck-Gesellschaft (MPG)
Helmholtz Association
Deutsche Zentrum für Lungenforschung (DZL)