Identification of the Hub Genes and the Signaling Pathways in Human iPSC-Cardiomyocytes Infected by SARS-CoV-2

Abstract

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSCcardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.

Application of hiPSC as a Drug Tester Via Mimicking a Personalized Mini Heart

“…During the worldwide outbreak of COVID-19, the hIPSC-CM-EHT model has contributed to several types of investigations that: 1) mimicked myocardial injuries caused by SARS-CoV-2 infection ( Li et al, 2021 ; Perez-Bermejo et al, 2021 ; Salerno et al, 2021 ; Xie et al, 2022 ); 2) evaluated the safety of different types of vaccines including mRNA and adenovirus vaccines, especially across different ethnic populations with different genomic backgrounds ( Bojkova et al, 2020 ; Lu et al, 2020 ; Davidson et al, 2021 ); and 3) assessed the potential side effects of anti-COVID-19 developed treatments on cardiomyocytes ( Charrez et al, 2021 ; Deguchi et al, 2021 ; Dimai et al, 2021 ). Research involving the hIPSC-CM-EHT model in COVID-19 has rapidly extended the application of hIPSC, making it a more common conceptual and powerful investigative tool.…”

Decoding HiPSC-CM’s Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury

“…The study by Navaratnarajah et al (2021) also compared the GSE184715 and GSE150392 datasets and found that SARS-CoV-2 infection of hiPSC-CMs resulted in a significant down-regulation of the expression of cardiomyocyte skeletal proteins [5]. In previous bioinformatics studies, the results of the analyses have been presented mechanistically without addressing the whole molecular biological process [6][7][8]. The novelty of this study is to appropriately portray the complete molecular biological process of SARS-CoV-2 infection of hiPSC-CMs at the bioinformatics level.…”

Natural Course of COVID-19 and Independent Predictors of Mortality

“…Most of them show that B-type natriuretic peptide (BNP) as a predictive marker of the severity of COVID-19 disease [ 11 ]. Thus, genes and signaling pathways involved in the myocardium infected by SARS-CoV-2 were subsequently identified highlighting the mechanisms underlying cardiac damage [ 12 ]. Furthermore, numerous studies have revealed a key role for the angiotensin converting enzyme-2 (ACE2) receptor, whose physiological balance is altered by SARS-CoV-2, by activating angiotensin II (Ang II)/Ang II receptor type 1 (AT1R) pathways and by leading to severe disease complications [ 13 , 14 ].…”