Abstract
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 methylation, 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.
【저자키워드】 COVID-19, SARS-CoV-2, Mitochondria, Single-cell transcriptomics, Methylation, Histones, 【초록키워드】 severe COVID-19, SARS-COV-2 infection, miRNA, Single-cell RNA sequencing, Regulatory, DNA, Clinical course, nasopharyngeal, Patient, Gene expression profiling, mechanisms, molecular, disease, Epigenetic, pathogenic mechanism, mechanism, cellular, Interaction, epithelial cell, membrane permeability, Activation, Regulation, ciliated cell, healthy control, sequence, upregulation, SARS-CoV-2 miRNAs, downregulation, gene expression signature, chromatin, misfolded proteins, scRNAseq, Mitochondrial function, objective, Result, the patient, addition, were used, analyses, explain, expand, histone methylation, pathway enrichment, patients with COVID-19, 【제목키워드】 severe COVID-19, nasal, Patient, Gene expression profiling, Epigenetic, mechanism, ciliated cell, Cell, reveal, biological processe,