Metabolic differences in MSTN and FGF5 dual-gene edited sheep muscle cells during myogenesis

• Published in: BMC genomics 2024-06, Vol.25 (1), p.637-14, Article 637
• Main Authors: Chen, Mingming, Li, Yan, Xu, Xueling, Wang, Shuqi, Liu, Zhimei, Qi, Shiyu, Si, Dandan, Man, Zhuo, Deng, Shoulong, Liu, Guoshi, Zhao, Yue, Yu, Kun, Lian, Zhengxing
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Animal models; Animals; Biomarkers; Biosynthesis; Cell culture; Cell Differentiation; Cells (biology); Data collection; Differentiation; Drug delivery; Drug development; Editing; Energy metabolism; Fatty acids; FGF5; Fibroblast growth factor 5; Fibroblast Growth Factor 5 - genetics; Fibroblast Growth Factor 5 - metabolism; Fibroblast growth factors; Fibroblasts; Gene Editing; Genes; Genetic aspects; Genetic modification; Genome editing; Genotype & phenotype; Growth factors; Hyperplasia; Lipid metabolism; Lipids; Mass spectrometry; Metabolism; Metabolites; Metabolomics; Monosaccharides; MSTN; Muscle Development - genetics; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Muscles; Musculoskeletal system; Mutation; Myogenesis; Myostatin; Myostatin - genetics; Myostatin - metabolism; Myotubes; Nucleotides; Oxidation; Pentose; Pentose phosphate pathway; Phosphates; Phosphorylation; Physiological aspects; Satellite cells; Satellite Cells, Skeletal Muscle - cytology; Satellite Cells, Skeletal Muscle - metabolism; Scientific imaging; Sheep; Skeketal muscle cells; Skeletal muscle; Software; Statistical analysis; Sugars; Tricarboxylic acid cycle; Unsaturated fatty acids
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-024-10494-w

Dynamic metabolic reprogramming occurs at different stages of myogenesis and contributes to the fate determination of skeletal muscle satellite cells (MuSCs). Accumulating evidence suggests that mutations in myostatin (MSTN) have a vital role in regulating muscle energy metabolism. Here, we explored the metabolic reprogramming in MuSCs and myotube cells in MSTN and FGF5 dual-gene edited sheep models prepared previously, and also focused on the metabolic alterations during myogenic differentiation of MuSCs. Our study revealed that the pathways of nucleotide metabolism, pantothenate and CoA biosynthesis were weakened, while the unsaturated fatty acids biosynthesis were strengthened during myogenic differentiation of sheep MuSCs. The MSTN and FGF5 dual-gene editing mainly inhibited nucleotide metabolism and biosynthesis of unsaturated fatty acids in sheep MuSCs, reduced the number of lipid droplets in per satellite cell, and promoted the pentose phosphate pathway, and the interconversion of pentose and glucuronate. The MSTN and FGF5 dual-gene editing also resulted in the inhibition of nucleotide metabolism and TCA cycle pathway in differentiated myotube cells. The differential metabolites we identified can be characterized as biomarkers of different cellular states, and providing a new reference for MSTN and FGF5 dual-gene editing in regulation of muscle development. It may also provide a reference for the development of muscle regeneration drugs targeting biomarkers.