Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection
Ma, Q; Ma, W; Song, TZ; Wu, Z; Liu, Z; Hu, Z; Han, JB; Xu, L; Zeng, B; Wang, B; Sun, Y; Yu, DD; Wu, Q; Yao, YG; Zheng, YT; Wang, X
2022
发表期刊ZOOLOGICAL RESEARCH
ISSN2095-8137
卷号43期号:6页码:1041-1062
摘要Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques (Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19.
收录类别sci
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/13480
专题科研部门_疾病机理遗传学和进化医学学科组(姚永刚)
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Ma, Q,Ma, W,Song, TZ,et al. Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection[J]. ZOOLOGICAL RESEARCH,2022,43(6):1041-1062.
APA Ma, Q.,Ma, W.,Song, TZ.,Wu, Z.,Liu, Z.,...&Wang, X.(2022).Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection.ZOOLOGICAL RESEARCH,43(6),1041-1062.
MLA Ma, Q,et al."Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection".ZOOLOGICAL RESEARCH 43.6(2022):1041-1062.
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