Single-cell transcriptomic atlas of primate cardiopulmonary aging

• 作者: Shuai Ma Shuhui Sun Jiaming Li Yanling Fan Jing Qu Liang Sun Si Wang Yiyuan Zhang Shanshan Yang Zunpeng Liu Zeming Wu Sheng Zhang Qiaoran Wang Aihua Zheng Shuguang Duo Yang Yu Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Moshi Song Weiqi Zhang Guang-Hui Liu
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: ARTICLES
• 页码范围: 415-432
• 页数: 18页
• 语种: 英文

摘要

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-KB-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.