A single-cell transcriptomic landscape of primate arterial aging
A single-cell transcriptomic landscape of primate arterial aging
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灵长类动物动脉衰老的单细胞转录组景观
DOI：
10.1038/s41467-020-15997-0
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发表时间：
2020-05-05
影响因子：
16.6
通讯作者：
Qu, Jing
中科院分区：
文献类型：
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作者：
Zhang, Weiqi;Zhang, Shu;Qu, Jing
我们对衰老如何影响脉管系统的细胞和分子成分的理解仍然有限。在这里，我们报告了年轻和老年cynomolgus猴子中主动脉和冠状动脉的单细胞转录组调查。我们的数据定义了专门动脉的分子特征，并确定了八个区分主动脉和冠状动脉血管的标记。基因网络分析了调节血管衰变和foxo3a的位置的转录标志，这是一种寿命相关的转录因子，是一种主调节基因，在衰老过程中六个亚基血管细胞亚型中下调。在人血管内皮细胞中FOXO3A的靶向失活概括了在老化的猴子动脉中观察到的主要表型缺陷，从而验证了FOXO3A损失是动脉内皮衰老的关键驱动因素。我们的研究为理解灵长类动脉衰老的原理提供了关键资源，并为未来与年龄相关的血管疾病的治疗提供了重要的线索。与心血管疾病紧密相关的动脉变性是由与衰老相关的血管细胞特异性转录组学变化驱动的。这项研究提供了一个用于老年主动脉和冠状动脉的单细胞转录图，并强调基于FOXO3A的转录网络在老化期间的血管保护中的转录网络。
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 positionFOXO3A, a longevity-associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation ofFOXO3Ain human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifyingFOXO3Aloss 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.