Gene Co-Expression Network Analysis Provides Novel Insights into Myostatin Regulation at Three Different Mouse Developmental Timepoints

Abstract

Myostatin (Mstn) knockout mice exhibit large increases in skeletal muscle mass. However, relatively few of the genes that mediate or modify MSTN effects are known. In this study, we performed co-expression network analysis using whole transcriptome microarray data from MSTN-null and wild-type mice to identify genes involved in important biological processes and pathways related to skeletal muscle and adipose development. Genes differentially expressed between wild-type and MSTN-null mice were further analyzed for shared DNA motifs using DREME. Differentially expressed genes were identified at 13.5 d.p.c. during primary myogenesis and at d35 during postnatal muscle development, but not at 17.5 d.p.c. during secondary myogenesis. In total, 283 and 2034 genes were differentially expressed at 13.5 d.p.c. and d35, respectively. Over-represented transcription factor binding sites in differentially expressed genes included SMAD3, SP1, ZFP187, and PLAGL1. The use of regulatory (RIF) and phenotypic (PIF) impact factor and differential hubbing co-expression analyses identified both known and potentially novel regulators of skeletal muscle growth, including Apobec2, Atp2a2, and Mmp13 at d35 and Sox2, Tmsb4x, and Vdac1 at 13.5 d.p.c. Among the genes with the highest PIF scores were many fiber type specifying genes. The use of RIF, PIF, and differential hubbing analyses identified both known and potentially novel regulators of muscle development. These results provide new details of how MSTN may mediate transcriptional regulation as well as insight into novel regulators of MSTN signal transduction that merit further study regarding their physiological roles in muscle and adipose development.

Developmental Stage, Muscle and Genetic Type Modify Muscle Transcriptome in Pigs: Effects on Gene Expression and Regulatory Factors Involved in Growth and Metabolism

“…ZIC1 and MMP13 are implicated in the early control of myogenesis and in myostatin signaling [109–112]. On the other hand, genes highly upregulated in BF muscle are involved in myogenesis control ( HOXA11 ), by regulating MYOD expression [113], muscle contraction ( PVALB ), or the immune response and adipocyte differentiation, [114].…”

Efficient TALEN-mediated myostatin gene editing in goats

“…Myostatin (encoded by the MSTN gene) is a member of the transforming growth factor family that acts as an important negative regulator of skeletal muscle growth [ 1 , 2 ]. Mutations in MSTN can inactivate its expression and result in a nonfunctional protein, which has great potential to enhance muscle growth, leading to dramatic muscularity and a “double-muscling” phenomenon in many species, including cattle [ 3 ], mice [ 4 ], humans [ 5 ], and sheep [ 6 ].…”

Integrative analysis of microRNAs and mRNAs involved in regulation of intramuscular fat deposition in Nelore cattle

“…The regulation of lipid oxidation and biosynthesis is under strong feedback control in order to maintain homeostasis [27]. Although research studying the influence of miRNAs on metabolism are recent [28], there has been a rapid growth in the number of identified miRNAs that are involved in the regulation of genes and signaling molecules responsible for maintaining lipid homeostasis [20,29].…”

“…They are related to lipolysis, i.e. in the oxidation of fatty acids, mainly described in skeletal muscle where their expression is higher [19,20]. On the other hand, PPARγ is mainly important for adipogenesis, promoting the proliferation and differentiation of adipocytes and also improve insulin sensitivity through increased liver and muscle glucose uptake and reduced circulation in the bloodstream [21].…”

“…The PCIT method identifies differences in pairs of correlated gene expression levels to measure a gene's differential connectivity across levels of a phenotype[17]. Both the PCIT and WGCNA approaches have enabled a better understanding of the co-regulation of mRNAs and miRNAs for different phenotypes[15,[18][19][20][21] to better comprehend the biological mechanisms and regulatory processes in lipid metabolism.The aim of this study was to identify candidate regulatory genes and pathways that are regulated by miRNAs and understand the importance of integrative co-expression networks of mRNAs-miRNAs for fat deposition in cattle from a systems biology perspective.…”