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Aging affects reprogramming of pulmonary capillary endothelial cells after lung injury in male mice

Marin Truchi, Marine Gautier-Isola, Grégoire Savary, Célia Scribe, Arun Lingampally, Hugo Cadis, Alberto Baeri, Virginie Magnone, Cédric Girard-Riboulleau, Marie-Jeanne Arguel, Clémentine Schutter, Julien Fassy, Nihad Boukrout, Romain Larrue, Nathalie Martin, Roger Rezzonico, Olivier Pluquet, Michael Perrais, Véronique Hofman, Charles-Hugo Marquette, Paul Hofman, Andreas Günther, Nicolas Ricard, Pascal Barbry, Sylvie Leroy, Kevin Lebrigand, Saverio Bellusci, Christelle Cauffiez, Georges Vassaux, Nicolas Pottier and Bernard Mari ()
Additional contact information
Marin Truchi: IPMC
Marine Gautier-Isola: IPMC
Grégoire Savary: UMR9020 CNRS - U1277 Inserm - CANTHER
Célia Scribe: IPMC
Arun Lingampally: Justus-Liebig-University (JLU)
Hugo Cadis: IPMC
Alberto Baeri: IPMC
Virginie Magnone: IPMC
Cédric Girard-Riboulleau: IPMC
Marie-Jeanne Arguel: IPMC
Clémentine Schutter: UMR9020 CNRS - U1277 Inserm - CANTHER
Julien Fassy: IPMC
Nihad Boukrout: UMR9020 CNRS - U1277 Inserm - CANTHER
Romain Larrue: UMR9020 CNRS - U1277 Inserm - CANTHER
Nathalie Martin: UMR9020 CNRS - U1277 Inserm - CANTHER
Roger Rezzonico: IPMC
Olivier Pluquet: UMR9020 CNRS - U1277 Inserm - CANTHER
Michael Perrais: UMR9020 CNRS - U1277 Inserm - CANTHER
Véronique Hofman: Université Côte d’Azur
Charles-Hugo Marquette: Université Côte d’Azur
Paul Hofman: Université Côte d’Azur
Andreas Günther: Justus-Liebig-University (JLU)
Nicolas Ricard: CEA
Pascal Barbry: IPMC
Sylvie Leroy: IPMC
Kevin Lebrigand: IPMC
Saverio Bellusci: Justus-Liebig-University (JLU)
Christelle Cauffiez: UMR9020 CNRS - U1277 Inserm - CANTHER
Georges Vassaux: IPMC
Nicolas Pottier: UMR9020 CNRS - U1277 Inserm - CANTHER
Bernard Mari: IPMC

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: Abstract Aging increases the risk of developing fibrotic diseases by hampering tissue regeneration after injury. Using longitudinal single-cell RNA-seq and spatial transcriptomics, here we compare the transcriptome of bleomycin (BLM) -induced fibrotic lungs of young and aged male mice, at 3 time points corresponding to the peak of fibrosis, regeneration, and resolution. We find that lung injury shifts the transcriptomic profiles of three pulmonary capillary endothelial cells (PCEC) subpopulations. The associated signatures are linked to pro-angiogenic signaling with strong Lrg1 expression and do not progress similarly throughout the resolution process between young and old animals. Moreover, part of this set of resolution-associated markers is also detected in PCEC from samples of patients with idiopathic pulmonary fibrosis. Finally, we find that aging also alters the transcriptome of PCEC, which displays typical pro-fibrotic and pro-inflammatory features. We propose that age-associated alterations in specific PCEC subpopulations may interfere with the process of lung progenitor differentiation, thus contributing to the persistent fibrotic process typical of human pathology.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62431-4

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DOI: 10.1038/s41467-025-62431-4

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