Year: 2020
Type: preprint
Abstract: ABSTRACT Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans. Bullet points We generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19. ACE2 + TMPRSS2 + epithelial cells of lung, kidney and liver are targets for SARS-CoV-2. ACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities. We unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry.
Authors: Lei Han, Xiaoyu Wei, Chuanyu Liu, Giacomo Volpe, Zhifeng Wang, Taotao Pan, Yue Yuan, Ying Lei, Yiwei Lai, Carl Ward, Yeya Yu, Mingyue Wang, Quan Shi, Tao Wu, Liang Wu, Ya Liu, Chunqing Wang, Yuanhang Zhang, Haixi Sun, Hao Yu, Zhenkun Zhuang, Tingting Tang, Yunting Huang, Haorong Lu, Liqin Xu, Jiangshan Xu, Mengnan Cheng, Yang Liu, Chi Wai Wong, Tao Tan, Weizhi Ji, Patrick H. Maxwell, Huanming Yang, Jian Wang, Shida Zhu, Shiping Liu, Xun Xu, Yong Hou, Miguel A. Esteban, Longqi Liu
Institutions: BGI Group (China), China National GeneBank, University of Chinese Academy of Sciences, Shenzhen Bay Laboratory, Chinese Academy of Sciences, Guangzhou Institutes of Biomedicine and Health, Zhengzhou University, University of Copenhagen, South China University of Technology, Suzhou Zelgen Biopharmaceuticals Co., Ltd. (China), Kunming University of Science and Technology, University of Cambridge, BGI Research
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G6023461509, G6589783354, G7823403734
OpenAlex ID: W3015352768