Abstract
DNA methylation is an important form of epigenetic regulation that can regulate the expression of genes and the development of tissues. Muscle satellite cells play an important role in skeletal muscle development and regeneration. Therefore, the DNA methylation status of genes in satellite cells is important in the regulation of the development of skeletal muscle. This study systematically investigated the changes of genome-wide DNA methylation in satellite cells during skeletal muscle development. According to the MeDIP-Seq data, 52,809–123,317 peaks were obtained for each sample, covering 0.70–1.79% of the genome. The number of reads and peaks was highest in the intron regions followed by the CDS regions. A total of 96,609 DMRs were identified between any two time points. Among them 6198 DMRs were annotated into the gene promoter regions, corresponding to 4726 DMGs. By combining the MeDIP-Seq and RNA-Seq data, a total of 202 overlap genes were obtained between DMGs and DEGs. GO and Pathway analysis revealed that the overlap genes were mainly involved in 128 biological processes and 23 pathways. Among the biological processes, terms related to regulation of cell proliferation and Wnt signaling pathway were significantly different. Gene–gene interaction analysis showed that Wnt5a, Wnt9a, and Tgfβ1 were the key nodes in the network. Furthermore, the expression level of Wnt5a, Wnt9a, and Tgfβ1 genes could be influenced by the methylation status of promoter region during skeletal muscle development. These results indicated that the Wnt and Tgfβ signaling pathways may play an important role in functional regulation of satellite cells, and the DNA methylation status of Wnt and Tgfβ signals is a key regulatory factor during skeletal muscle development. This study provided new insights into the effects of genome-wide methylation on the function of satellite cells.
Highlights
Skeletal muscle satellite cells are a kind of mononuclear cells with a flattened projection, which locate between the muscle fiber basement membrane and the muscle cell membrane in skeletal muscle (Mauro, 1961)
The result showed that the overlap genes were enriched in 23 signaling pathways (p < 0.05), some of which were related to muscle development, including Calcium signaling pathway, Wnt signaling pathway, and Insulin secretion (Figure 4B). These results indicated that the DNA methylation status in satellite cells plays an important role in the development of skeletal muscle
Q-PCR result showed that the expression level of Wnt9a gene was significantly up-regulated at Week 6, but down-regulated from Weeks 8 to 12 (Figure 6F). These results indicated that the expression level of Wnt5a, Wnt9a, and Tgfβ1 genes could be influenced by the methylation state of promoter region during skeletal muscle development
Summary
Skeletal muscle satellite cells are a kind of mononuclear cells with a flattened projection, which locate between the muscle fiber basement membrane and the muscle cell membrane in skeletal muscle (Mauro, 1961). Satellite cells can be activated, and undergo myogenic differentiation to form new muscle fibers or to fuse with myotubes to repair damaged areas, when muscle fibers are damaged (Collins et al, 2005; Guitart et al, 2018). Researches showed that the activation, proliferation, and differentiation of satellite cells play a critical role in skeletal muscle development, which require the involvement of a variety of signaling molecules, including TGF pathway (Delaney et al, 2017), FGF pathway (Han et al, 2012), and Wnt pathway (Girardi and Le Grand, 2018). Studies showed that TGFβ1 could inhibit the proliferation of myoblasts and the regeneration of necrotic muscle fibers, and Wnt signaling could regulate the differentiation of myoblast by interacting with TGFβ signaling (Melone et al, 1999; Rudolf et al, 2016). The epigenetic regulatory mechanism affecting the expression level of these key factors remain largely unknown
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
