Comparison of Gene Expression Patterns Associated with Myostatin Using Transcriptomic Data of the Myogenic C۲C۱۲ Cell Line and Skeletal Muscle Tissue

TGF-β group member myostatin (MSTN) inhibits the growth and differentiation of skeletal muscle. It is unknown how total inhibition of MSTN restricts the hyperproliferation of muscle cells, though. This study aimed to determine the differentially expressed genes and biological pathways associated with myostatin in mouse C۲C۱۲ myogenic cells and skeletal muscle tissue, utilizing high-throughput mRNA expression data. In both tissue and cell line, two experimental groups were compared, including wild-type vs. MSTN-Knockout. Transcriptome data were extracted from GEO and analyzed using the LIMMA package in the R environment and GEO۲R. Significantly differentially expressed genes were considered as adjusted p-value < ۰.۰۵ with log fold change > |۰.۵|. Lastly, the possible biological pathways were examined with the KEGG database, and the protein-protein interaction (PPI) network was created using Cytoscape software. To find key genes in the PPI network, a topological analysis was conducted using the Network Analyzer tool in Cytoscape software. The total number of differentially expressed genes was ۱۴۵۴۹ for the C۲C۱۲ cell line and ۴۵۲۶۷ for mouse skeletal muscle tissue; among them, ۲۳۵ and ۱۴۲۵ transcripts were significant with an adjusted p-value <۰.۰۵. The comparison between these two DEG lists showed that ۴۹ genes were common between the myogenic C۲C۱۲ cell and skeletal muscle tissue. Additionally, three biological pathways between the C۲C۱۲ cell line and the skeletal muscle tissue were in common, and they were associated with the decrease of MSTN gene expression, including: hypertrophic cardiomyopathy, Axon guidance, and dilated cardiomyopathy. These pathways were all related to muscle tissue. Despite the large number of DEGs, only ۴۹ were in common in tissue and cell line; this could indicate that comparing a tissue with its relevant cell line at the transcriptome level might not be precise enough to draw a solid conclusion. This is due to the nature of cell heterogeneity of most tissues, including skeletal muscle.

کلیدواژه ها:

Myostatin ، mouse ، Gene Network ، C۲C۱۲ cell line ، tissue muscle