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Single-cell transcriptomic atlas of primate cardiopulmonary aging.
Cell Research ( IF 44.1 ) Pub Date : 2020-09-10 , DOI: 10.1038/s41422-020-00412-6
Shuai Ma 1, 2, 3 , Shuhui Sun 1, 4 , Jiaming Li 5, 6, 7 , Yanling Fan 5, 6, 7 , Jing Qu 2, 3, 7 , Liang Sun 8, 9 , Si Wang 1, 3, 10 , Yiyuan Zhang 4 , Shanshan Yang 10 , Zunpeng Liu 2, 7 , Zeming Wu 2, 7 , Sheng Zhang 4, 7 , Qiaoran Wang 5, 6, 7 , Aihua Zheng 7, 11 , Shuguang Duo 12 , Yang Yu 13, 14 , Juan Carlos Izpisua Belmonte 15 , Piu Chan 10 , Qi Zhou 2, 3, 7 , Moshi Song 2, 3, 7 , Weiqi Zhang 5, 6, 7 , Guang-Hui Liu 1, 3, 4, 7, 10
Affiliation  

Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.



中文翻译:

灵长类动物心肺衰老的单细胞转录组图谱。

衰老是许多疾病的主要风险因素,尤其是在高度流行的心肺合并症和包括 2019 年冠状病毒病 (COVID-19) 在内的传染病中。因此,迫切需要解决与高等哺乳动物衰老相关的细胞和分子机制。在这里,我们创建了肺、心脏和动脉的年轻和年老非人类灵长类动物单核/细胞转录组图谱,这是 SARS-CoV-2 靶向的顶级组织。对细胞类型特异性衰老相关转录变化的分析表明,全身炎症增加和病毒防御受损是心肺衰老的标志。随着年龄的增长,肺泡上皮屏障、心肌细胞和血管内皮细胞中 SARS-CoV-2 受体血管紧张素转换酶 2 (ACE2) 的表达增加。我们发现白细胞介素 7 (IL7) 在老年心肺组织中积累,并以 NF-κB 依赖性方式诱导人血管内皮细胞中 ACE2 的表达。此外,维生素 C 治疗阻断了 IL7 诱导的 ACE2 表达。总而言之,我们的研究结果描绘了老年灵长类动物心肺系统的第一个转录组图谱,并为与年龄相关的 SARS-CoV-2 易感性提供了重要见解,这表明老年保护策略可能会降低老年人 COVID-19 的严重程度。

更新日期:2020-09-11
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