PuSH - Publication Server of Helmholtz Zentrum München: Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Lang, N.J. ; Schniering, J. ; Porras-Gonzalez, D.L. ; Yang, L. ; De Sadeleer, L.J. ; Jentzsch, R.C. ; Shitov, V.A. ; Zhou, S. ; Ansari, M. ; Agami, A. ; Mayr, C. ; Hooshiar Kashani, B. ; Chen, Y. ; Heumos, L. ; Pestoni, J. ; Molnar, E.S. ; Geeraerts, E.* ; Anquetil, V.* ; Saniere, L.* ; Wögrath, M. ; Gerckens, M. ; Lehmann, M. ; Yildirim, A.Ö. ; Hatz, R.A.* ; Kneidinger, N. ; Behr, J. ; Wuyts, W.A.* ; Stoleriu, M.-G. ; Luecken, M. ; Theis, F.J. ; Burgstaller, G. ; Schiller, H.

Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Sci. Transl. Med. 15, 19:eadh0908 (2023)

DOI

PMC

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS. We showed that these cell states were highly similar to the in vivo cell circuit in a multicohort lung cell atlas from patients with pulmonary fibrosis. Using micro-CT-staged patient tissues, we characterized the appearance and interaction of myofibroblasts, an ectopic endothelial cell state, and basaloid epithelial cells in the thickened alveolar septum of early-stage lung fibrosis. Induction of these states in the hPCLS model provided evidence that the basaloid cell state was derived from alveolar type 2 cells, whereas the ectopic endothelial cell state emerged from capillary cell plasticity. Cell-cell communication routes in patients were largely conserved in hPCLS, and antifibrotic drug treatments showed highly cell type-specific effects. Our work provides an experimental framework for perturbational single-cell genomics directly in human lung tissue that enables analysis of tissue homeostasis, regeneration, and pathology. We further demonstrate that hPCLS offer an avenue for scalable, high-resolution drug testing to accelerate antifibrotic drug development and translation.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Idiopathic Pulmonary-fibrosis; Pirfenidone; Deficiency; Nintedanib

ISSN (print) / ISBN 1946-6234

e-ISSN 1946-6242

Journal Science Translational Medicine

Quellenangaben Volume: 15, Issue: 725, Pages: 19, Article Number: eadh0908

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
Institute of Lung Biology (LHI)

Grants Bundesinstitut fur Risikoforschung
Deutsche Forschungsgemeinschaft
German Center for Lung Research
Helmholtz Association
European Respiratory Society
Faculty of Medicine of the Ludwig-Maximilians-University Munich
Bavarian State Ministry of Science and Arts
Chan Zuckerberg Initiative
European Union