A Single-cell Transcriptomic Landscape of the Lungs of Patients with COVID-19

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2021 Dec 8

PMID 34876692

Citations 91

Authors

Si Wang

Xiaohong Yao

Shuai Ma

Yifang Ping

Yanling Fan

Shuhui Sun

Zhicheng He

Yu Shi

Liang Sun

Shiqi Xiao

Moshi Song

Jun Cai

Jiaming Li

Rui Tang

Liyun Zhao

Chaofu Wang

Qiaoran Wang

Lei Zhao

Huifang Hu

Xindong Liu

Guoqiang Sun

Lu Chen

Guoqing Pan

Huaiyong Chen

Qingrui Li

Peipei Zhang

Yuanyuan Xu

Huyi Feng

Guo-Guang Zhao

Tianzi Wen

Yungui Yang

Xuequan Huang

Wei Li

Zhenhua Liu

Hongmei Wang

Haibo Wu

Baoyang Hu

Yong Ren

Qi Zhou

Jing Qu

Weiqi Zhang

Guang-Hui Liu

Xiu-Wu Bian

Affiliations

Soon will be listed here.

Abstract

The lung is the primary organ targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making respiratory failure a leading coronavirus disease 2019 (COVID-19)-related mortality. However, our cellular and molecular understanding of how SARS-CoV-2 infection drives lung pathology is limited. Here we constructed multi-omics and single-nucleus transcriptomic atlases of the lungs of patients with COVID-19, which integrate histological, transcriptomic and proteomic analyses. Our work reveals the molecular basis of pathological hallmarks associated with SARS-CoV-2 infection in different lung and infiltrating immune cell populations. We report molecular fingerprints of hyperinflammation, alveolar epithelial cell exhaustion, vascular changes and fibrosis, and identify parenchymal lung senescence as a molecular state of COVID-19 pathology. Moreover, our data suggest that FOXO3A suppression is a potential mechanism underlying the fibroblast-to-myofibroblast transition associated with COVID-19 pulmonary fibrosis. Our work depicts a comprehensive cellular and molecular atlas of the lungs of patients with COVID-19 and provides insights into SARS-CoV-2-related pulmonary injury, facilitating the identification of biomarkers and development of symptomatic treatments.

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