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  • 标题:PPARγ Cistrome Repression during Activation of Lung Monocyte-Macrophages in Severe COVID-19
  • 本地全文:下载
  • 作者:Christophe Desterke ; Ali G. Turhan ; Annelise Bennaceur-Griscelli
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2020
  • 卷号:23
  • 期号:10
  • 页码:1-45
  • DOI:10.1016/j.isci.2020.101611
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryThe molecular mechanisms of cytokine storm in patients with severe COVID-19 infections are poorly understood. To uncover these events, we performed transcriptome analyses of lung biopsies from patients with COVID-19, revealing a gene enrichment pattern similar to that of PPARγ-knockout macrophages. Single-cell gene expression analysis of bronchoalveolar lavage fluids revealed a characteristic trajectory of PPARγ-related disturbance in the CD14+/CD16+ cells. We identified a correlation with the disease severity and the reduced expression of several members of the PPARγ complex such as EP300, RXRA, RARA, SUMO1, NR3C1, and CCDC88A. ChIP-seq analyses confirmed repression of the PPARγ-RXRA-NR3C1 cistrome in COVID-19 lung samples. Further analysis of protein-protein networks highlighted an interaction between the PPARγ-associated protein SUMO1 and a nucleoprotein of the SARS virus. Overall, these results demonstrate for the first time the involvement of the PPARγ complex in severe COVID-19 lung disease and suggest strongly its role in the major monocyte/macrophage-mediated inflammatory storm.Graphical AbstractDisplay OmittedHighlights•PPARγ expression is repressed in inflammatory lungs of patients with severe COVID-19•PPARγ trajectory is disrupted in bronchoalveolar CD14+/CD16+ cells of patients with COVID-19•We report here the epigenetics repression of PPARγ-NR3R1-RXRA cistrome in this setting•SUMO1, as repressed PPARγ partner, interacts with nucleoprotein of the human SARS virusImmunology; Viral Microbiology; Transcriptomics
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