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Kadri, S. ; Fischer, A. ; Mück-Häusl, M. ; Han, W. ; Kadri, A. ; Lin, Y. ; Yang, L. ; Hu, S. ; Ye, H. ; Ramesh, P. ; Ansari, M. ; Schiller, H.B. ; Machens, H.G.* ; Rinkevich, Y.*

A mesothelial differentiation gateway drives fibrosis.

Nat. Commun. 16:8295 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Internal organs are encased by a supportive epithelial monolayer of mesodermal origin, termed mesothelium. The nature, evolution and function of mesothelial cells, and their genetic regulation impacting disease development are insufficiently understood. Here, we generate a comprehensive organ-wide single-cell transcriptomic compendium of mesothelium across healthy and diseased mouse and human organs, delineating the evolution of conserved activated states of mesothelial cells in response to disease. We uncover genetic drives behind each cell state and reveal a conserved metabolic gate into multipotent proteolytic, inflammatory and fibrotic cell differentiation, in mouse and human. Using lung injury models in mice, in combination with mesothelial cell-specific viral approaches, we show that direct metabolic reprogramming using Ifi27l2a and Crip1 on organ surfaces, blocks multipotent differentiation and protects mouse lungs from fibrotic disease. These findings place mesothelial cells as cellular exemplars and gateway to fibrotic disease, opening translational approaches to subvert fibrosis across a range of clinical indications.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cells; Health
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 16, Heft: 1, Seiten: , Artikelnummer: 8295 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Regenerative Biology and Medicine (IRBM)
Research Unit Precision Regenerative Medicine (PRM)
Institute of Diabetes and Cancer (IDC)
POF Topic(s) 30202 - Environmental Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Lung Research
Environmental Sciences
Helmholtz Diabetes Center
PSP-Element(e) G-509400-001
G-507300-001
G-501900-251
Förderungen LEO Foundation
European Research Council
DOI 10.1038/s41467-025-63990-2
WOS ID 001573937500014
Scopus ID 105016423184
PubMed ID 40957887
Erfassungsdatum 2025-10-21
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