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Volume 43 Issue 6
Nov.  2022
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Article Navigation >  Zoological Research  > 2022  >  43(6): 1041-1062
Qiang Ma, Wenji Ma, Tian-Zhang Song, Zhaobo Wu, Zeyuan Liu, Zhenxiang Hu, Jian-Bao Han, Ling Xu, Bo Zeng, Bosong Wang, Yinuo Sun, Dan-Dan Yu, Qian Wu, Yong-Gang Yao, Yong-Tang Zheng, Xiaoqun Wang. Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection. Zoological Research, 2022, 43(6): 1041-1062. doi: 10.24272/j.issn.2095-8137.2022.443
Citation: Qiang Ma, Wenji Ma, Tian-Zhang Song, Zhaobo Wu, Zeyuan Liu, Zhenxiang Hu, Jian-Bao Han, Ling Xu, Bo Zeng, Bosong Wang, Yinuo Sun, Dan-Dan Yu, Qian Wu, Yong-Gang Yao, Yong-Tang Zheng, Xiaoqun Wang. Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection. Zoological Research, 2022, 43(6): 1041-1062. doi: 10.24272/j.issn.2095-8137.2022.443
shu

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

doi: 10.24272/j.issn.2095-8137.2022.443
  • 1.

    State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

  • 2.

    University of Chinese Academy of Sciences, Beijing 100049, China

  • 3.

    Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China

  • 4.

    Kunming National High-Level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China

  • 5.

    National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China

  • 6.

    LivzonBio, Inc., Zhuhai, Guangdong 519045, China

  • 7.

    State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China

  • 8.

    IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China

  • 9.

    Advanced Innovation Center for Human Brain Protection, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China

The raw sequencing data used in this study were deposited in the Genome Sequence Archive (GSA) database of the National Genomics Data Center (NGDC) under accession number CRA006787, Gene Expression Omnibus (GEO) of the NCBI under accession number GSE217483, and Science Data Bank (doi:10.57760/sciencedb.06252). All other data supporting the findings of this study are available from the corresponding author upon reasonable request.
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
X.W., Y.T.Z., and Y.G.Y. conceived the project and designed the experiments. T.Z.S., Z.H., J.B.H., L.X., and D.D.Y. constructed the animal model and collected the samples. Q.M. and Z.L. performed the single-nucleus RNA-seq experiments. W.M., Z.W., B.Z., and Y.S. analyzed the RNA-seq data. Q.M. and B.W. performed tissue sectioning and immunostaining. Q.M., W.M., and Q.W. wrote the manuscript and all authors edited and proofed the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work
Funds:  This work was supported by the National Basic Research Program of China (2020YFA0804000, 2020YFC0842000, 2020YFA0112200, 2021YFC2301703); Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32010100); Special Associate Research Program of the Chinese Academy of Sciences (E1290601); National Natural Science Foundation of China (32122037, 81891001, 32192411, 32100512, U1902215); Collaborative Research Fund of the Chinese Institute for Brain Research, Beijing (2020-NKX-PT-03); CAS Project for Young Scientists in Basic Research (YSBR-013); Young Elite Scientist Sponsorship Program by the China Association for Science and Technology (2020QNRC001); and National Resource Center for Non-Human Primates
More Information
    Abstract
  • 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.
    • The raw sequencing data used in this study were deposited in the Genome Sequence Archive (GSA) database of the National Genomics Data Center (NGDC) under accession number CRA006787, Gene Expression Omnibus (GEO) of the NCBI under accession number GSE217483, and Science Data Bank (doi:10.57760/sciencedb.06252). All other data supporting the findings of this study are available from the corresponding author upon reasonable request.
    Supplementary data to this article can be found online.
    The authors declare that they have no competing interests.
    X.W., Y.T.Z., and Y.G.Y. conceived the project and designed the experiments. T.Z.S., Z.H., J.B.H., L.X., and D.D.Y. constructed the animal model and collected the samples. Q.M. and Z.L. performed the single-nucleus RNA-seq experiments. W.M., Z.W., B.Z., and Y.S. analyzed the RNA-seq data. Q.M. and B.W. performed tissue sectioning and immunostaining. Q.M., W.M., and Q.W. wrote the manuscript and all authors edited and proofed the manuscript. All authors read and approved the final version of the manuscript.
    #Authors contributed equally to this work
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  • [1]
    Adams S, Braidy N, Bessesde A, Brew BJ, Grant R, Teo C, et al. 2012. The kynurenine pathway in brain tumor pathogenesis. Cancer Research, 72(22): 5649−5657. doi: 10.1158/0008-5472.CAN-12-0549
    [2]
    Aibar S, González-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, et al. 2017. SCENIC: single-cell regulatory network inference and clustering. Nature Methods, 14(11): 1083−1086. doi: 10.1038/nmeth.4463
    [3]
    Aydin MF, Yıldız A, Oruç A, Sezen M, Dilek K, Güllülü M, et al. 2021. Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccination. Kidney International, 100(2): 464−465. doi: 10.1016/j.kint.2021.05.001
    [4]
    Banerjee A, Macdonald ML, Borgmann-Winter KE, Hahn CG. 2010. Neuregulin 1-erbB4 pathway in schizophrenia: from genes to an interactome. Brain Research Bulletin, 83(3–4): 132–139.
    [5]
    Bayati A, Kumar R, Francis V, Mcpherson PS. 2021. SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis. Journal of Biological Chemistry, 296: 100306. doi: 10.1016/j.jbc.2021.100306
    [6]
    Beckers CML, Van Hinsbergh VWM, Van Nieuw Amerongen GP. 2010. Driving Rho GTPase activity in endothelial cells regulates barrier integrity. Thrombosis and Haemostasis, 103(1): 40−55. doi: 10.1160/TH09-06-0403
    [7]
    Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. 2020. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell, 181(5): 1036−1045.e9. doi: 10.1016/j.cell.2020.04.026
    [8]
    Boiko DI, Skrypnikov AM, Shkodina AD, Hasan MM, Ashraf GM, Rahman MH. 2022. Circadian rhythm disorder and anxiety as mental health complications in post-COVID-19. Environmental Science and Pollution Research, 29(19): 28062−28069. doi: 10.1007/s11356-021-18384-4
    [9]
    Boyer JL. 2013. Bile formation and secretion. Comprehensive Physiology, 3(3): 1035−1078.
    [10]
    Brooks AK, Lawson MA, Smith RA, Janda TM, Kelley KW, Mccusker RH. 2016. Interactions between inflammatory mediators and corticosteroids regulate transcription of genes within the Kynurenine pathway in the mouse hippocampus. Journal of Neuroinflammation, 13(1): 98. doi: 10.1186/s12974-016-0563-1
    [11]
    Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. 2018. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nature Biotechnology, 36(5): 411−420. doi: 10.1038/nbt.4096
    [12]
    Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, et al. 2020. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science, 370(6518): 856−860. doi: 10.1126/science.abd2985
    [13]
    Cao JY, Spielmann M, Qiu XJ, Huang XF, Ibrahim DM, Hill AJ, et al. 2019. The single-cell transcriptional landscape of mammalian organogenesis. Nature, 566(7745): 496−502. doi: 10.1038/s41586-019-0969-x
    [14]
    Cao X, Li WJ, Wang T, Ran DZ, Davalos V, Planas-Serra L, et al. 2022. Accelerated biological aging in COVID-19 patients. Nature Communications, 13(1): 2135. doi: 10.1038/s41467-022-29801-8
    [15]
    Caza TN, Hassen SI, Dvanajscak Z, Kuperman M, Edmondson R, Herzog C, et al. 2021. NELL1 is a target antigen in malignancy-associated membranous nephropathy. Kidney International, 99(4): 967−976. doi: 10.1016/j.kint.2020.07.039
    [16]
    Chen BJ, Lamb RA. 2008. Mechanisms for enveloped virus budding: can some viruses do without an ESCRT?. Virology, 372(2): 221−232. doi: 10.1016/j.virol.2007.11.008
    [17]
    Chen EY, Tan CM, Kou Y, Duan QN, Wang ZC, Meirelles GV, et al. 2013. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics, 14: 128. doi: 10.1186/1471-2105-14-128
    [18]
    Chen PG, Li J, Huo Y, Lu J, Wan LL, Li B, et al. 2015. Orphan nuclear receptor NR4A2 inhibits hepatic stellate cell proliferation through MAPK pathway in liver fibrosis. PeerJ, 3: e1518. doi: 10.7717/peerj.1518
    [19]
    Cheng YC, Luo R, Wang K, Zhang M, Wang ZX, Dong L, et al. 2020. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney International, 97(5): 829−838. doi: 10.1016/j.kint.2020.03.005
    [20]
    Coleman PR, Lay AJ, Ting KK, Zhao Y, Li J, Jarrah S, et al. 2020. YAP and the RhoC regulator ARHGAP18, are required to mediate flow-dependent endothelial cell alignment. Cell Communication and Signaling, 18(1): 18. doi: 10.1186/s12964-020-0511-7
    [21]
    Cravedi P. 2021. Complement in membranous nephropathy: what we thought we knew and what we really know. Kidney International, 100(3): 499−501. doi: 10.1016/j.kint.2021.03.010
    [22]
    Crawley JTB, Zanardelli S, Chion CKNK, Lane DA. 2007. The central role of thrombin in hemostasis. Journal of Thrombosis and Haemostasis, 5 Suppl 1: 95–101.
    [23]
    Csortos C, Czikora I, Bogatcheva NV, Adyshev DM, Poirier C, Olah G, et al. 2008. TIMAP is a positive regulator of pulmonary endothelial barrier function. American Journal of Physiology-Lung Cellular and Molecular Physiology, 295(3): L440−L450. doi: 10.1152/ajplung.00325.2007
    [24]
    Daniloski Z, Jordan TX, Wessels HH, Hoagland DA, Kasela S, Legut M, et al. 2021. Identification of required host factors for SARS-CoV-2 infection in human cells. Cell, 184(1): 92−105.e16. doi: 10.1016/j.cell.2020.10.030
    [25]
    David S, Kümpers P, Van Slyke P, Parikh SM. 2013. Mending leaky blood vessels: the angiopoietin-Tie2 pathway in sepsis. Journal of Pharmacology and Experimental Therapeutics, 345(1): 2−6. doi: 10.1124/jpet.112.201061
    [26]
    Debruin EJ, Hughes MR, Sina C, Lu A, Cait J, Jian ZQ, et al. 2014. Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion. PLoS One, 9(10): e108881. doi: 10.1371/journal.pone.0108881
    [27]
    Delorey TM, Ziegler CGK, Heimberg G, Normand R, Yang YM, Segerstolpe Å, et al. 2021. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature, 595(7865): 107−113. doi: 10.1038/s41586-021-03570-8
    [28]
    Deng JW, Zhou FW, Hou WT, Silver Z, Wong CY, Chang O, et al. 2021. The prevalence of depression, anxiety, and sleep disturbances in COVID-19 patients: a meta-analysis. Annals of the New York Academy of Sciences, 1486(1): 90−111. doi: 10.1111/nyas.14506
    [29]
    Deng W, Bao LL, Gao H, Xiang ZG, Qu YJ, Song ZQ, et al. 2020. Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in rhesus macaques. Nature Communications, 11(1): 4400. doi: 10.1038/s41467-020-18149-6
    [30]
    Dinatale BC, Murray IA, Schroeder JC, Flaveny CA, Lahoti TS, Laurenzana EM, et al. 2010. Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicological Sciences, 115(1): 89−97. doi: 10.1093/toxsci/kfq024
    [31]
    Dostal CR, Gamsby NS, Lawson MA, Mccusker RH. 2018. Glia- and tissue-specific changes in the Kynurenine pathway after treatment of mice with lipopolysaccharide and dexamethasone. Brain, Behavior, and Immunity, 69: 321−335. doi: 10.1016/j.bbi.2017.12.006
    [32]
    Efremova M, Vento-Tormo M, Teichmann SA, Vento-Tormo R. 2020. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nature Protocols, 15(4): 1484−1506. doi: 10.1038/s41596-020-0292-x
    [33]
    Escartin C, Galea E, Lakatos A, O'Callaghan JP, Petzold GC, Serrano-Pozo A, et al. 2021. Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience, 24(3): 312−325. doi: 10.1038/s41593-020-00783-4
    [34]
    Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, et al. 2002. T cell apoptosis by tryptophan catabolism. Cell Death & Differentiation, 9(10): 1069−1077.
    [35]
    Fan CF, Wu Y, Rui X, Yang YS, Ling C, Liu SS, et al. 2022. Animal models for COVID-19: advances, gaps and perspectives. Signal Transduction and Targeted Therapy, 7(1): 220. doi: 10.1038/s41392-022-01087-8
    [36]
    Fu Y, Zhu R, Bai T, Han P, He Q, Jing MJ, et al. 2021. Clinical features of patients infected with coronavirus disease 2019 with elevated liver biochemistries: a multicenter, retrospective study. Hepatology, 73(4): 1509−1520. doi: 10.1002/hep.31446
    [37]
    Galani IE, Rovina N, Lampropoulou V, Triantafyllia V, Manioudaki M, Pavlos E, et al. 2021. Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nature Immunology, 22(1): 32−40. doi: 10.1038/s41590-020-00840-x
    [38]
    Gao Q, Bao LL, Mao HY, Wang L, Xu KW, Yang MN, et al. 2020. Development of an inactivated vaccine candidate for SARS-CoV-2. Science, 369(6499): 77−81. doi: 10.1126/science.abc1932
    [39]
    Givertz MM. 2001. Manipulation of the renin-angiotensin system. Circulation, 104(5): e14−e18.
    [40]
    Goñalons E, Barrachina M, García-Sanz JA, Celada A. 1998. Translational control of MHC class II I-A molecules by IFN-γ. Journal of Immunology, 161(4): 1837−1843.
    [41]
    Guo WW, Tan PH, Baikunje S. 2022. Membranous nephropathy in a patient with COVID-19 infection. Journal of Nephrology, 35(1): 351−355. doi: 10.1007/s40620-021-01165-0
    [42]
    Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. 2020. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science, 369(6504): 718−724. doi: 10.1126/science.abc6027
    [43]
    He JP, Cai SJ, Feng HJ, Cai BM, Lin LH, Mai Y, et al. 2020. Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients. Protein & Cell, 11(9): 680−687.
    [44]
    Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. 2020. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181(2): 271−280.e8. doi: 10.1016/j.cell.2020.02.052
    [45]
    Huang CL, Huang LX, Wang YM, Li X, Ren LL, Gu XY, et al. 2021. 6-Month consequences of COVID-19 in patients discharged from hospital: a cohort study. The Lancet, 397(10270): 220−232. doi: 10.1016/S0140-6736(20)32656-8
    [46]
    Huang HH, Bhat A, Woodnutt G, Lappe R. 2010. Targeting the ANGPT-TIE2 pathway in malignancy. Nature Reviews Cancer, 10(8): 575−585. doi: 10.1038/nrc2894
    [47]
    Irons EE, Punch PR, Lau JTY. 2020. Blood-borne ST6GAL1 regulates immunoglobulin production in B cells. Frontiers in Immunology, 11: 617. doi: 10.3389/fimmu.2020.00617
    [48]
    Jenabian MA, El-Far M, Vyboh K, Kema I, Costiniuk CT, Thomas R, et al. 2015. Immunosuppressive tryptophan catabolism and gut mucosal dysfunction following early HIV infection. Journal of Infectious Diseases, 212(3): 355−366. doi: 10.1093/infdis/jiv037
    [49]
    Jin HJ, Zhang YR, You HY, Tao XM, Wang C, Jin GZ, et al. 2015. Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration and invasion of human hepatocellular carcinoma. Scientific Reports, 5: 10466. doi: 10.1038/srep10466
    [50]
    Jin SQ, Guerrero-Juarez CF, Zhang LH, Chang I, Ramos R, Kuan CH, et al. 2021. Inference and analysis of cell-cell communication using CellChat. Nature Communications, 12(1): 1088. doi: 10.1038/s41467-021-21246-9
    [51]
    Kassiri Z, Oudit GY, Kandalam V, Awad A, Wang XH, Ziou X, et al. 2009. Loss of TIMP3 enhances interstitial nephritis and fibrosis. Journal of the American Society of Nephrology, 20(6): 1223−1235. doi: 10.1681/ASN.2008050492
    [52]
    Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, et al. 2020. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host & Microbe, 27(5): 704−709.e2.
    [53]
    Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, et al. 2019. Fast, sensitive and accurate integration of single-cell data with Harmony. Nature Methods, 16(12): 1289−1296. doi: 10.1038/s41592-019-0619-0
    [54]
    Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan QN, Wang ZC, et al. 2016. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Research, 44(W1): W90−W97. doi: 10.1093/nar/gkw377
    [55]
    Laug D, Huang TW, Huerta NAB, Huang AYS, Sardar D, Ortiz-Guzman J, et al. 2019. Nuclear factor I-A regulates diverse reactive astrocyte responses after CNS injury. The Journal of Clinical Investigation, 129(10): 4408−4418. doi: 10.1172/JCI127492
    [56]
    Lawler NG, Gray N, Kimhofer T, Boughton B, Gay M, Yang RC, et al. 2021. Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses. Journal of Proteome Research, 20(5): 2796−2811. doi: 10.1021/acs.jproteome.1c00052
    [57]
    Lee GK, Park HJ, Macleod M, Chandler P, Munn DH, Mellor AL. 2002. Tryptophan deprivation sensitizes activated T cells to apoptosis prior to cell division. Immunology, 107(4): 452−460. doi: 10.1046/j.1365-2567.2002.01526.x
    [58]
    Lee J, Gravel M, Zhang RL, Thibault P, Braun PE. 2005. Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein. Journal of Cell Biology, 170(4): 661−673. doi: 10.1083/jcb.200411047
    [59]
    Lee JS, Koh JY, Yi K, Kim YI, Park SJ, Kim EH, et al. 2021. Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets. Nature Communications, 12(1): 4567. doi: 10.1038/s41467-021-24807-0
    [60]
    Lehrman EK, Wilton DK, Litvina EY, Welsh CA, Chang ST, Frouin A, et al. 2018. CD47 protects synapses from excess microglia-mediated pruning during development. Neuron, 100(1): 120−134.e6. doi: 10.1016/j.neuron.2018.09.017
    [61]
    Li MT, Di W, Xu H, Yang YK, Chen HW, Zhang FX, et al. 2013. Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1. Journal of Virology, 87(18): 10037−10046. doi: 10.1128/JVI.01073-13
    [62]
    Li SB, Li L, Wu JY, Song FB, Qin ZW, Hou L, et al. 2020. TDO promotes hepatocellular carcinoma progression. OncoTargets and Therapy, 13: 5845−5855. doi: 10.2147/OTT.S252929
    [63]
    Liang C, Tao YM, Shen CY, Tan Z, Xiong WC, Mei L. 2012. Erbin is required for myelination in regenerated axons after injury. Journal of Neuroscience, 32(43): 15169−15180. doi: 10.1523/JNEUROSCI.2466-12.2012
    [64]
    Liang W, Mao SS, Sun SJ, Li M, Li Z, Yu R, et al. 2018. Core fucosylation of the T cell receptor is required for T cell activation. Frontiers in Immunology, 9: 78. doi: 10.3389/fimmu.2018.00078
    [65]
    Lionetto L, Ulivieri M, Capi M, De Bernardini D, Fazio F, Petrucca A, et al. 2021. Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: an observational cohort study. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1867(3): 166042. doi: 10.1016/j.bbadis.2020.166042
    [66]
    Liu Q, Shi Y, Cai J, Duan YQ, Wang RS, Zhang HY, et al. 2020a. Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases. National Science Review, 7(12): 1868−1878. doi: 10.1093/nsr/nwaa247
    [67]
    Liu Q, Zhai J, Kong XY, Wang XY, Wang ZZ, Fang Y, et al. 2020b. Comprehensive analysis of the expression and prognosis for TDO2 in breast cancer. Molecular Therapy Oncolytics, 17: 153−168. doi: 10.1016/j.omto.2020.03.013
    [68]
    Liu YH, Wang YR, Wang QH, Chen Y, Chen X, Li Y, et al. 2021. Post-infection cognitive impairments in a cohort of elderly patients with COVID-19. Molecular Neurodegeneration, 16(1): 48. doi: 10.1186/s13024-021-00469-w
    [69]
    Liu YY, Liang XY, Dong WQ, Fang Y, Lv JD, Zhang TZ, et al. 2018. Tumor-repopulating cells induce PD-1 expression in CD8+ T cells by transferring kynurenine and AhR activation. Cancer Cell, 33(3): 480−494.e7. doi: 10.1016/j.ccell.2018.02.005
    [70]
    Ma L, Xu B, Wang WJ, Deng WP, Ding M. 2009. Analysis of tryptophan catabolism in HBV patients by HPLC with programmed wavelength ultraviolet detection. Clinica Chimica Acta, 405(1–2): 94–96.
    [71]
    Ma S, Sun SH, Li JM, Fan YL, Qu J, Sun L, et al. 2021. Single-cell transcriptomic atlas of primate cardiopulmonary aging. Cell Research, 31(4): 415−432. doi: 10.1038/s41422-020-00412-6
    [72]
    Mao L, Jin HJ, Wang MD, Hu Y, Chen SC, He QW, et al. 2020. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurology, 77(6): 683−690. doi: 10.1001/jamaneurol.2020.1127
    [73]
    Mavrikaki M, Lee JD, Solomon IH, Slack FJ. 2021. Severe COVID-19 induces molecular signatures of aging in the human brain. medRxiv,doi: 10.1101/2021.11.24.21266779.
    [74]
    Melms JC, Biermann J, Huang HC, Wang YP, Nair A, Tagore S, et al. 2021. A molecular single-cell lung atlas of lethal COVID-19. Nature, 595(7865): 114−119. doi: 10.1038/s41586-021-03569-1
    [75]
    Merad M, Blish CA, Sallusto F, Iwasaki A. 2022. The immunology and immunopathology of COVID-19. Science, 375(6585): 1122−1127. doi: 10.1126/science.abm8108
    [76]
    Mezrich JD, Fechner JH, Zhang XJ, Johnson BP, Burlingham WJ, Bradfield CA. 2010. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. The Journal of Immunology, 185(6): 3190−3198. doi: 10.4049/jimmunol.0903670
    [77]
    Morita K, Sasaki H, Fujimoto K, Furuse M, Tsukita S. 1999. Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. The Journal of Cell Biology, 145(3): 579−588. doi: 10.1083/jcb.145.3.579
    [78]
    Muñoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, Riveros-Balta AX, Albrecht RA, et al. 2020. Animal models for COVID-19. Nature, 586(7830): 509−515. doi: 10.1038/s41586-020-2787-6
    [79]
    Munster VJ, Feldmann F, Williamson BN, Van Doremalen N, Pérez-Pérez L, Schulz J, et al. 2020. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature, 585(7824): 268−272. doi: 10.1038/s41586-020-2324-7
    [80]
    Muus C, Luecken MD, Eraslan G, Sikkema L, Waghray A, Heimberg G, et al. 2021. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nature Medicine, 27(3): 546−559. doi: 10.1038/s41591-020-01227-z
    [81]
    Nelson CE, Namasivayam S, Foreman TW, Kauffman KD, Sakai S, Dorosky DE, et al. 2022. Mild SARS-CoV-2 infection in rhesus macaques is associated with viral control prior to antigen-specific T cell responses in tissues. Science Immunology, 7: eabo0535. doi: 10.1126/sciimmunol.abo0535
    [82]
    Nevler A, Muller AJ, Sutanto-Ward E, Duhadaway JB, Nagatomo K, Londin E, et al. 2019. Host IDO2 gene status influences tumor progression and radiotherapy response in KRAS-driven sporadic pancreatic cancers. Clinical Cancer Research, 25(2): 724−734. doi: 10.1158/1078-0432.CCR-18-0814
    [83]
    Nie QH, Duan GR, Luo XD, Xie YM, Luo H, Zhou YX, et al. 2004. Expression of TIMP-1 and TIMP-2 in rats with hepatic fibrosis. World Journal of Gastroenterology, 10(1): 86−90. doi: 10.3748/wjg.v10.i1.86
    [84]
    Okazawa H, Motegi SI, Ohyama N, Ohnishi H, Tomizawa T, Kaneko Y, et al. 2005. Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. The Journal of Immunology, 174(4): 2004−2011. doi: 10.4049/jimmunol.174.4.2004
    [85]
    Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, et al. 2011. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature, 478(7368): 197−203. doi: 10.1038/nature10491
    [86]
    Palumbo-Zerr K, Zerr P, Distler A, Fliehr J, Mancuso R, Huang JG, et al. 2015. Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis. Nature Medicine, 21(2): 150−158. doi: 10.1038/nm.3777
    [87]
    Pan XW, Xu D, Zhang H, Zhou W, Wang LH, Cui XG. 2020. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Medicine, 46(6): 1114−1116. doi: 10.1007/s00134-020-06026-1
    [88]
    Pei GC, Zhang ZG, Peng J, Liu L, Zhang CX, Yu C, et al. 2020. Renal involvement and early prognosis in patients with COVID-19 pneumonia. Journal of the American Society of Nephrology, 31(6): 1157−1165. doi: 10.1681/ASN.2020030276
    [89]
    Pekny M, Pekna M. 2014. Astrocyte reactivity and reactive astrogliosis: costs and benefits. Physiological Reviews, 94(4): 1077−1098. doi: 10.1152/physrev.00041.2013
    [90]
    Pizzini A, Kurz K, Santifaller J, Tschurtschenthaler C, Theurl I, Fuchs D, et al. 2019. Assessment of neopterin and indoleamine 2, 3-dioxygenase activity in patients with seasonal influenza: a pilot study. Influenza and Other Respiratory Viruses, 13(6): 603−609. doi: 10.1111/irv.12677
    [91]
    Rad Pour S, Morikawa H, Kiani NA, Yang MY, Azimi A, Shafi G, et al. 2019. Exhaustion of CD4+ T-cells mediated by the Kynurenine pathway in melanoma. Scientific Reports, 9(1): 12150. doi: 10.1038/s41598-019-48635-x
    [92]
    Ren XW, Wen W, Fan XY, Hou WH, Su B, Cai PF, et al. 2021. COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell, 184(7): 1895−1913.e19. doi: 10.1016/j.cell.2021.01.053
    [93]
    Ronco P, Beck L, Debiec H, Fervenza FC, Hou FF, Jha V, et al. 2021. Membranous nephropathy. Nature Reviews Disease Primers, 7(1): 69. doi: 10.1038/s41572-021-00303-z
    [94]
    Saichi M, Ladjemi MZ, Korniotis S, Rousseau C, Ait Hamou Z, Massenet-Regad L, et al. 2021. Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity. Nature Cell Biology, 23(5): 538−551. doi: 10.1038/s41556-021-00681-2
    [95]
    Santhanam S, Alvarado DM, Ciorba MA. 2016. Therapeutic targeting of inflammation and tryptophan metabolism in colon and gastrointestinal cancer. Translational Research, 167(1): 67−79. doi: 10.1016/j.trsl.2015.07.003
    [96]
    Schuster V, Hügle B, Tefs K. 2007. Plasminogen deficiency. Journal of Thrombosis and Haemostasis, 5(12): 2315−2322. doi: 10.1111/j.1538-7836.2007.02776.x
    [97]
    Scudellari M. 2021. How the coronavirus infects cells - and why delta is so dangerous. Nature, 595(7869): 640−644. doi: 10.1038/d41586-021-02039-y
    [98]
    Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, et al. 2006. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. American Journal of Respiratory and Critical Care Medicine, 173(2): 188−198. doi: 10.1164/rccm.200504-644OC
    [99]
    Sethi S, Debiec H, Madden B, Charlesworth MC, Morelle J, Gross L, et al. 2020. Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney International, 97(1): 163−174. doi: 10.1016/j.kint.2019.09.014
    [100]
    Shan C, Yao YF, Yang XL, Zhou YW, Gao G, Peng Y, et al. 2020. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques. Cell Research, 30(8): 670–677.
    [101]
    Simmons G, Zmora P, Gierer S, Heurich A, Pöhlmann S. 2013. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Research, 100(3): 605−614. doi: 10.1016/j.antiviral.2013.09.028
    [102]
    Singh M, Bansal V, Feschotte C. 2020. A single-cell RNA expression map of human coronavirus entry factors. Cell Reports, 32(12): 108175. doi: 10.1016/j.celrep.2020.108175
    [103]
    Skinner JA, Zurawski SM, Sugimoto C, Vinet-Oliphant H, Vinod P, Xue YM, et al. 2014. Immunologic characterization of a rhesus macaque H1N1 challenge model for candidate influenza virus vaccine assessment. Clinical and Vaccine Immunology, 21(12): 1668−1680. doi: 10.1128/CVI.00547-14
    [104]
    Song TZ, Zheng HY, Han JB, Feng XL, Liu FL, Yang X, et al. 2021. Northern pig-tailed macaques (Macaca leonina) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response. Zoological Research, 42(3): 350−353. doi: 10.24272/j.issn.2095-8137.2020.334
    [105]
    Song TZ, Zheng HY, Han JB, Jin L, Yang X, Liu FL, et al. 2020. Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques. Zoological Research, 41(5): 503−516. doi: 10.24272/j.issn.2095-8137.2020.202
    [106]
    Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al. 2020. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney International, 98(1): 219−227. doi: 10.1016/j.kint.2020.04.003
    [107]
    Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, et al. 2020. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine, 26(5): 681−687. doi: 10.1038/s41591-020-0868-6
    [108]
    Thomas T, Stefanoni D, Reisz JA, Nemkov T, Bertolone L, Francis RO, et al. 2020. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI Insight, 5(14): e140327. doi: 10.1172/jci.insight.140327
    [109]
    Thompson MG, Muñoz-Moreno R, Bhat P, Roytenberg R, Lindberg J, Gazzara MR, et al. 2018. Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing. Nature Communications, 9(1): 2407. doi: 10.1038/s41467-018-04779-4
    [110]
    Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. 2020. Endothelial cell infection and endotheliitis in COVID-19. The Lancet, 395(10234): 1417−1418. doi: 10.1016/S0140-6736(20)30937-5
    [111]
    Wang DW, Hu B, Hu C, Zhu FF, Liu X, Zhang J, et al. 2020a. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 323(11): 1061−1069. doi: 10.1001/jama.2020.1585
    [112]
    Wang H, Zhang YT, Huang BY, Deng W, Quan YR, Wang WL, et al. 2020b. Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2. Cell, 182(3): 713−721.e9. doi: 10.1016/j.cell.2020.06.008
    [113]
    Wang S, Yao XH, Ma S, Ping YF, Fan YL, Sun SH, et al. 2021. A single-cell transcriptomic landscape of the lungs of patients with COVID-19. Nature Cell Biology, 23(12): 1314−1328. doi: 10.1038/s41556-021-00796-6
    [114]
    Werion A, Belkhir L, Perrot M, Schmit G, Aydin S, Chen ZY, et al. 2020. SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule. Kidney International, 98(5): 1296−1307. doi: 10.1016/j.kint.2020.07.019
    [115]
    Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. 2020. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA, 324(8): 782−793. doi: 10.1001/jama.2020.12839
    [116]
    Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ, Mckechnie JL, et al. 2020. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nature Medicine, 26(7): 1070−1076. doi: 10.1038/s41591-020-0944-y
    [117]
    Wolf FA, Angerer P, Theis FJ. 2018. SCANPY: large-scale single-cell gene expression data analysis. Genome Biology, 19(1): 15. doi: 10.1186/s13059-017-1382-0
    [118]
    Wolock SL, Lopez R, Klein AM. 2019. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Systems, 8(4): 281−291.e9. doi: 10.1016/j.cels.2018.11.005
    [119]
    Wu H, Gong JP, Liu Y. 2018. Indoleamine 2, 3-dioxygenase regulation of immune response (review). Molecular Medicine Reports, 17(4): 4867−4873.
    [120]
    Xie YL, Su N, Yang J, Tan QY, Huang S, Jin M, et al. 2020. FGF/FGFR signaling in health and disease. Signal Transduction and Targeted Therapy, 5(1): 181. doi: 10.1038/s41392-020-00222-7
    [121]
    Xu L, Yu DD, Ma YH, Yao YL, Luo RH, Feng XL, et al. 2020. COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2. Zoological Research, 41(5): 517−526. doi: 10.24272/j.issn.2095-8137.2020.053
    [122]
    Yang AC, Kern F, Losada PM, Agam MR, Maat CA, Schmartz GP, et al. 2021. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature, 595(7868): 565−571. doi: 10.1038/s41586-021-03710-0
    [123]
    Yano T, Mason RJ, Pan TL, Deterding RR, Nielsen LD, Shannon JM. 2000. KGF regulates pulmonary epithelial proliferation and surfactant protein gene expression in adult rat lung. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279(6): L1146−L1158. doi: 10.1152/ajplung.2000.279.6.L1146
    [124]
    Yao YF, Bao LL, Deng W, Xu LL, Li FD, Lv Q, et al. 2014. An animal model of MERS produced by infection of rhesus macaques with MERS coronavirus. The Journal of Infectious Diseases, 209(2): 236−242. doi: 10.1093/infdis/jit590
    [125]
    Yoo JS, Sasaki M, Cho SX, Kasuga Y, Zhu BH, Ouda R, et al. 2021. SARS-CoV-2 inhibits induction of the MHC class I pathway by targeting the STAT1-IRF1-NLRC5 axis. Nature Communications, 12(1): 6602. doi: 10.1038/s41467-021-26910-8
    [126]
    Zahr A, Alcaide P, Yang JL, Jones A, Gregory M, Dela Paz NG, et al. 2016. Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions. Nature Communications, 7: 10363. doi: 10.1038/ncomms10363
    [127]
    Zhang Q, Bastard P, Liu ZY, Le Pen J, Moncada-Velez M, Chen J, et al. 2020. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, 370(6515): eabd4570. doi: 10.1126/science.abd4570
    [128]
    Zhou F. 2009. Molecular mechanisms of IFN-γ to up-regulate MHC class I antigen processing and presentation. International Reviews of Immunology, 28(3–4): 239–260.
    [129]
    Zhou FH, Wan QY, Chen S, Chen Y, Wang PH, Yao X, et al. 2021. Attenuating innate immunity and facilitating β-coronavirus infection by NSP1 of SARS-CoV-2 through specific redistributing hnRNP A2/B1 cellular localization. Signal Transduction and Targeted Therapy, 6(1): 371. doi: 10.1038/s41392-021-00786-y
    [130]
    Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798): 270−273. doi: 10.1038/s41586-020-2012-7
    [131]
    Zhu H, Wang GH, Qian J. 2016. Transcription factors as readers and effectors of DNA methylation. Nature Reviews Genetics, 17(9): 551−565. doi: 10.1038/nrg.2016.83
    [132]
    Zhu JM, Li KX, Cao SX, Chen XJ, Shen CJ, Zhang Y, et al. 2017. Increased NRG1-ErbB4 signaling in human symptomatic epilepsy. Scientific Reports, 7(1): 141. doi: 10.1038/s41598-017-00207-7
    [133]
    Zhu Q, Tan Z, Zhao SF, Huang H, Zhao XF, Hu XM, et al. 2015. Developmental expression and function analysis of protein tyrosine phosphatase receptor type D in oligodendrocyte myelination. Neuroscience, 308: 106−114. doi: 10.1016/j.neuroscience.2015.08.062
    [134]
    Zoupi L, Savvaki M, Kalemaki K, Kalafatakis I, Sidiropoulou K, Karagogeos D. 2018. The function of contactin-2/TAG-1 in oligodendrocytes in health and demyelinating pathology. Glia, 66(3): 576−591. doi: 10.1002/glia.23266
    [135]
    Zuchero JB, Fu MM, Sloan SA, Ibrahim A, Olson A, Zaremba A, et al. 2015. CNS myelin wrapping is driven by actin disassembly. Developmental Cell, 34(2): 152−167. doi: 10.1016/j.devcel.2015.06.011
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