Exploring Primate Arterial Aging Through Single-Cell Transcriptomics
Summary
It is still unclear how aging impacts the cellular and molecular components of the vasculature and contributes to cardiovascular diseases. They present a single-cell transcriptomic study of young and old cynomolgus monkey aortas and coronary arteries. They found eight markers distinguishing aortic and coronary vasculatures and defined the molecular signatures of specialized arteries. Gene network analyses identify transcriptional landmarks that regulate vascular senility and identify FOXO3A, a longevity-associated transcription factor, as a master regulator gene downregulated in six monkey vascular cell subtypes during aging. Targeted FOXO3A inactivation in human vascular endothelial cells replicates the major phenotypic defects observed in aged monkey arteries, confirming FOXO3A loss as a key driver of arterial endothelial aging. Their research is crucial to understanding primate arterial aging and treating age-related vascular disorders.
Fig.1 Working model. (Zhang, 2020)
Research Criteria
The researchers obtain a single-cell transcriptomic atlas of the atherosclerosis-prone aortic arch and coronary artery in young and aged cynomolgus monkeys. Based on this dataset, they identify distinct molecular signatures that illustrate the cell diversity of the aorta and coronary artery. Moreover, they reveal cell-type-specific modifications to the molecular programs of the aging primate vasculature. In addition, they identify FOXO3A as a key protective factor for primate vascular homeostasis. Targeted inactivation of FOXO3A in human arterial vascular endothelial cells (ECs), which disrupt cellular homeostasis, replicates the most prominent phenotypic defects observed in aged monkey arteries.
Fig.2 Method flowchart. (Zhang, 2020)
Sample Type
Isolated coronary arteries and aortic arches from the monkey heart. After tissue digestion, using FACS (Fluorescence-Activated Cell Sorting) to enrich CD31+ and CD45- ECs (Endothelial Cells).
Result—scRNA-Seq Analysis of Young and Old Monkey Aortic and Coronary Arteries
To examine the subpopulation structure and molecular characteristics of the aged monkey vasculature, scRNA-seq was performed on lesion-prone aortas and coronary arteries from eight young (age, 4-6 years) and eight old (age, 18-21 years) cynomolgus monkeys. Consistent with the enrichment strategy and anatomical regions, the arterial tunica intima, media, and adventitia could be mapped to nine distinct cell clusters isolated from vascular wall cells.
Fig.3 Cell clusters and cell type expression signatures. (Zhang, 2020)
Result—Site-Specific Gene Expression Signatures of Aortic and Coronary Arteries
They then compared the aortic and coronary artery single cell transcriptomes. Circos plots revealed that aortic and coronary cells exhibited site-specific signatures of gene expression, which were predominantly shared by cell populations from the same vascular bed. A panel of location-specific genes was differentially expressed in aortic and coronary Asterias cells, as determined by immunofluorescence analysis. These findings defined the molecular landscape underlying the adaptation of vascular organotypicity to region-specific arterial functions.
Fig.4 Survey of scRNA expression of cells from the aortic artery and the coronary artery. (Zhang, 2020)
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Reference
- Zhang, W.; et al. A single-cell transcriptomic landscape of primate arterial aging. Nature Communications. 2020, 11: 2202.
