作者: |
Wang,Si;Yao,Xiaohong;Ma,Shuai;Ping,Yifang;Fan,Yanling;Sun,Shuhui;He,Zhicheng;Shi,Yu;Sun,Liang;Xiao,Shiqi;Song,Moshi;Cai,Jun;Li,Jiaming;Tang,Rui;Zhao,Liyun;Wang,Chaofu;Wang,Qiaoran;Zhao,Lei;Hu,Huifang;Liu,Xindong;Sun,Guoqiang;Chen,Lu;Pan,Guoqing;Chen,Huaiyong;Li,Qingrui;Zhang,Peipei;Xu,Yuanyuan;Feng,Huyi;Zhao,Guo-Guang;Wen,Tianzi;Yang,Yungui;Huang,Xuequan;Li,Wei;Liu,Zhenhua;Wang,Hongmei;Wu,Haibo;Hu,Baoyang;Ren,Yong;Zhou,Qi;Qu,Jing;Zhang,Weiqi;Liu,Guang-Hui;Bian,Xiu-Wu |
摘要: |
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.Wang et al. analysed post-mortem samples of the lungs of patients with COVID-19 by bulk and single-nucleus RNA sequencing along with proteomics and discovered lung senescence as a feature of COVID-19 pathology. |