Complementary transcriptome and proteome analysis of dystrophin-deficient satellite cells

Introduction There is a paucity of studies on dystrophin-deficiency in myogenic satellite cells (SC) and their contribution to Duchenne Muscular Dystrophy (DMD). Hence, this study was launched to evaluate the behaviour of SC outside their niche and thus unaffected from a pathologic environment to reveal intrinsic changes and differentiation at precontractile status.

Material and Methods SC were isolated from intercostalis and pectoralis muscles from 3-days-old male DMD^Y/- (n=4), female carrier HET (n=4) and age-matched WT (n=4) pigs. SC were cultivated in-vitro and harvested for transcriptome and proteome analysis both in a proliferative state (PROL) and after differentiation into multinucleated myotubes (DIFF). Subsequently, 3’ mRNA sequencing and liquid chromatography tandem mass spectrometry were performed.

Results Transcriptome and proteome profiles of PROL and DIFF state of DMD^Y/- SC separated from WT & HET SC. Altogether 568 differentially expressed genes were identified in PROL SC and 822 in DIFF SC. Proteome analysis revealed 453 proteins with altered abundance in PROL SC and 808 in DIFF SC.

Conclusions SC from DMD^Y/- animals show essential differences to WT and HET at transcriptional and protein level. Abnormalities start right at the onset of myogenesis, demonstrating that dystrophin exerts an essential role in muscle differentiation, far before the cells is exposed to contraction forces.

Publication History

Article published online:
26 June 2024