Aging affects reprogramming of pulmonary capillary endothelial cells after lung injury in male mice
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.
Article Details
Authors (31)
Marin Truchi
Marine Gautier-Isola
Grégoire Savary
Célia Scribe
Arun Lingampally
Hugo Cadis
Alberto Baeri
Virginie Magnone
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Cédric Girard-Riboulleau
Marie-Jeanne Arguel
Clémentine de 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
Biosanté unit U1292, Grenoble Alpes University, INSERM, CEA
Pascal Barbry
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Sylvie Leroy
Kevin Lebrigand
Université Côte d'Azur, CNRS, INSERM, Institut de Pharmacologie Moléculaire et Cellulaire
Saverio Bellusci
Christelle Cauffiez
Georges Vassaux
Nicolas Pottier
Bernard Mari