Volume 31, No 4, Apr 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 4, April 2021: 415-432   |  Open Access

ORIGINAL ARTICLES

Single-cell transcriptomic atlas of primate cardiopulmonary aging

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 Zhang⁴ , Shanshan Yang¹⁰ , Zunpeng Liu^2,7 , Zeming Wu^2,7 , Sheng Zhang^4,7 , Qiaoran Wang^5,6,7 , Aihua Zheng^7,11 , Shuguang Duo¹² , Yang Yu^13,14 , 4, Juan Carlos Izpisua Belmonte¹⁵ , Piu Chan¹⁰ , Qi Zhou^2,3,7 , Moshi Song^2,3,7,* , Weiqi Zhang^5,6,7,* , Guang-Hui Liu^1,3,4,7,10,*

¹State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
²State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
³Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
⁴National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
⁵CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
⁶China National Center for Bioinformation, Beijing 100101, China
⁷University of Chinese Academy of Sciences, Beijing 100049, China
⁸The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
⁹NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, Yunnan 650223, China
¹⁰Advanced Innovation Center for Human Brain Protection, and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China
¹¹State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
¹²Laboratory Animal Center, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
¹³Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
¹⁴Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China
¹⁵Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
These authors contributed equally: Shuai Ma, Shuhui Sun, Jiaming Li, Yanling Fan, Jing Qu, Liang Sun Correspondence: Moshi Song(songmoshi@ioz.ac.cn)Weiqi Zhang(zhangwq@big.ac.cn)Guang-Hui Liu(ghliu@ioz.ac.cn)

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.

https://doi.org/10.1038/s41422-020-00412-6

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