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Single-Cell Transcriptome Identifies the Renal Cell Type Tropism of Human BK Polyomavirus

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机构: [1]Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. [2]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. [3]Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou 510080, China. [4]Guangdong Provincial International Cooperation Based of Science and Technology (Organ Transplantation), Sun Yat-Sen University, Guangzhou 510080, China. [5]Department of Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510080, China.
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关键词: BK polyomavirus single-cell transcriptomics tropism immune microenvironment metabolism multi-omics

摘要:
BK polyomavirus (BKPyV) infection is the main factor affecting the prognosis of kidney transplant recipients, as no antiviral agent is yet available. A better understanding of the renal-cell-type tropism of BKPyV can serve to develop new treatment strategies. In this study, the single-cell transcriptomic analysis demonstrated that the ranking of BKPyV tropism for the kidney was proximal tubule cells (PT), collecting duct cells (CD), and glomerular endothelial cells (GEC) according to the signature of renal cell type and immune microenvironment. In normal kidneys, we found that BKPyV infection-related transcription factors P65 and CEBPB were PT-specific transcription factors, and PT showed higher glycolysis/gluconeogenesis activities than CD and GEC. Furthermore, in the BKPyV-infected kidneys, the percentage of late viral transcripts in PT was significantly higher than in CD and GEC. In addition, PT had the smallest cell-cell interactions with immune cells compared to CD and GEC in both normal and BKPyV-infected kidneys. Subsequently, we indirectly demonstrated the ranking of BKPyV tropism via the clinical observation of sequential biopsies. Together, our results provided in-depth insights into the renal cell-type tropism of BKPyV in vivo at single-cell resolution and proposed a novel antiviral target.

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 2 区 化学:综合 3 区 生化与分子生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 3 区 化学:综合
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出版当年[2021]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CHEMISTRY, MULTIDISCIPLINARY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CHEMISTRY, MULTIDISCIPLINARY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者:
第一作者机构: [1]Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. [2]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China. [3]Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou 510080, China. [4]Guangdong Provincial International Cooperation Based of Science and Technology (Organ Transplantation), Sun Yat-Sen University, Guangzhou 510080, China.
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通讯机构: [1]Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. [3]Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou 510080, China. [4]Guangdong Provincial International Cooperation Based of Science and Technology (Organ Transplantation), Sun Yat-Sen University, Guangzhou 510080, China.
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