4.7 Article

Single cell gene expression profiling of nasal ciliated cells reveals distinctive biological processes related to epigenetic mechanisms in patients with severe COVID-19

期刊

COMPUTERS IN BIOLOGY AND MEDICINE
卷 148, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.compbiomed.2022.105895

关键词

Single-cell transcriptomics; COVID-19; Histones; Methylation; SARS-CoV-2; Mitochondria

资金

  1. Agencia Nacional de Promocion Cientifica y Tecnologica, FONCYT [PICT 2018-889, PICT 2019-0528, PICT 2016-0135, PICT 2018-0620, PICT 2018-03713]
  2. CONICET [PUE 0055]

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This study used single-cell RNA sequencing to analyze ciliated cells from patients with mild/moderate and severe COVID-19, and found upregulation of gene expression signatures associated with mitochondrial function, misfolded proteins, and membrane permeability in mild/moderate cases, as well as downregulation of epigenetic mechanisms in severe cases. Additionally, the study identified miRNAs that may be involved in histone methylation regulation and share similarities with SARS-CoV-2 miRNAs.
Objective: To explore the molecular processes associated with cellular regulatory programs in patients with COVID-19, including gene activation or repression mediated by epigenetic mechanisms. We hypothesized that a comprehensive gene expression profiling of nasopharyngeal epithelial cells might expand our understanding of the pathogenic mechanisms of severe COVID-19.Methods: We used single-cell RNA sequencing (scRNAseq) profiling of ciliated cells (n = 12,725) from healthy controls (SARS-CoV-2 negative n = 13) and patients with mild/moderate (n = 13) and severe (n = 14) COVID-19. ScRNAseq data at the patient level were used to perform gene set and pathway enrichment analyses. We prioritized candidate miRNA-target interactions and epigenetic mechanisms. Results: We found that mild/moderate COVID-19 compared to healthy controls had upregulation of gene expression signatures associated with mitochondrial function, misfolded proteins, and membrane permeability. In addition, we found that compared to mild/moderate disease, severe COVID-19 had downregulation of epigenetic mechanisms, including DNA and histone H3K4 methylation and chromatin remodelling regulation. Furthermore, we found 11-ranked miRNAs that may explain miRNA-dependent regulation of histone methyl-ation, some of which share seed sequences with SARS-CoV-2 miRNAs.Conclusion: Our results may provide novel insights into the epigenetic mechanisms mediating the clinical course of SARS-CoV-2 infection.

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