A single-cell transcriptomic landscape of the lungs of patients with COVID-19.

A single-cell transcriptomic landscape of the lungs of patients with COVID-19.
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COVID-19 患者肺部的单细胞转录组图景

DOI:
10.1038/s41556-021-00796-6
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发表时间:
2021-12
影响因子:
21.3
通讯作者:
Bian XW
Bian XW
中科院分区:
生物学1区
文献类型:
--
作者:
Wang S;Yao X;Ma S;Ping Y;Fan Y;Sun S;He Z;Shi Y;Sun L;Xiao S;Song M;Cai J;Li J;Tang R;Zhao L;Wang C;Wang Q;Zhao L;Hu H;Liu X;Sun G;Chen L;Pan G;Chen H;Li Q;Zhang P;Xu Y;Feng H;Zhao GG;Wen T;Yang Y;Huang X;Li W;Liu Z;Wang H;Wu H;Hu B;Ren Y;Zhou Q;Qu J;Zhang W;Liu GH;Bian XW

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肺是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的主要靶器官,使呼吸衰竭成为2019年冠状病毒病(COVID-19)相关死亡率的主要原因。然而,我们对SARS-CoV-2感染如何驱动肺部病理的细胞和分子理解是有限的。在这里,我们构建了COVID-19患者肺部的多组学和单核转录组图谱,其中整合了组织学,转录组学和蛋白质组学分析。我们的工作揭示了与SARS-CoV-2感染相关的不同肺和浸润免疫细胞群的病理标志的分子基础。我们报告了炎症过度、肺泡上皮细胞衰竭、血管变化和纤维化的分子指纹,并将肺实质衰老确定为COVID-19病理学的分子状态。此外,我们的数据表明,FOXO 3A抑制是与COVID-19肺纤维化相关的成纤维细胞向肌成纤维细胞转化的潜在机制。我们的工作描绘了COVID-19患者肺部的全面细胞和分子图谱,并提供了对SARS-CoV-2相关肺损伤的见解,促进了生物标志物的鉴定和对症治疗的开发。
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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