Aging affects reprogramming of murine pulmonary capillary endothelial cells after lung injury

Truchi, M., Gautier-Isola, M., Savary, G., Cadis, H., Scribe, C., Baeri, A., Lingampally, A., Magnone, V., Girard-Riboulleau, C., Arguel, M.-J., de Schutter, C., Fassy, J., Boukrout, N., Larrue, R., Martin, N., Rezzonico, R., Pluquet, O., Perrais, M., Hofman, V., Marquette, C.-H., Hofman, P., Günther, A., Ricard, N., BARBRY, P., Leroy, S., Lebrigand, K., Bellusci, S., Cauffiez, C., Vassaux, G., Pottier, N., Mari, B.

IPMC, UMR7275 CNRS Côte d\\\'Azur University, Valbonne France · biorxiv

Paper

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-induced fibrotic lungs of young and aged 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 display 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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the effects of aging on pulmonary capillary endothelial cells in the context of lung injury and fibrosis, which is relevant to understanding age-related changes in tissue regeneration and the underlying mechanisms contributing to age-associated diseases. While it provides solid insights into the transcriptomic alterations linked to aging and fibrosis, the findings appear to be incremental rather than groundbreaking, limiting its overall impact on the field of longevity research.

Author of this paper? Send a correction.