1. A single-cell transcriptomic landscape of primate arterial aging
- Author
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Jie Ren, Piu Chan, Si Wang, Hongyu Li, Jinghui Lei, Shu Zhang, Shuai Ma, Fei Sun, Jing Qu, Jingyi Li, Qi Zhou, Xibo Ma, Wei Li, Pengze Yan, Guang-Hui Liu, Haifeng Wan, Huize Pan, Fuchou Tang, Weiqi Zhang, and Moshi Song
- Subjects
0301 basic medicine ,Aging ,Endothelium ,Science ,Gene regulatory network ,General Physics and Astronomy ,Article ,General Biochemistry, Genetics and Molecular Biology ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,medicine ,Animals ,Primate ,Transcriptomics ,lcsh:Science ,Vascular diseases ,Gene ,Transcription factor ,Aorta ,Multidisciplinary ,biology ,Forkhead Box Protein O3 ,Endothelial Cells ,General Chemistry ,Coronary Vessels ,Phenotype ,Coronary arteries ,Macaca fascicularis ,Ageing ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Q ,Endothelium, Vascular ,Single-Cell Analysis ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. Here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize transcriptional landmarks that regulate vascular senility and position FOXO3A, a longevity-associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders., Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.
- Published
- 2020