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 C2C12 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 GEO2R. Significantly differentially expressed genes were considered as adjusted p-value < 0.05 with log fold change > |0.5|. 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 14549 for the C2C12 cell line and 45267 for mouse skeletal muscle tissue; among them, 235 and 1425 transcripts were significant with an adjusted p-value <0.05. The comparison between these two DEG lists showed that 49 genes were common between the myogenic C2C12 cell and skeletal muscle tissue. Additionally, three biological pathways between the C2C12 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 49 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.

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