Modeling of myogenesis using human embryonic stem cells reveals myotonic dystrophy type 1 specific misregulated cellular processes

RNA sequencing

We report the analysis of RNA sequencing results performed on human embryonic stem cells, carrying the myotonic dystrophy type 1 (DM1) mutation naturally, and their derived myoblasts and myotubes. The goal of the study was to reveal DM1-specific mechanisms during early myogenic development. After RNAseq analysis we found a subtle aberrant inflammation response in DM1 myoblasts possibly leading to an abnormal myotube formation thereafter. In addition an increased CpG methylation pattern upstream of the DM1 mutation was found and RNA missplicing events start to be abundantly present from the myotube stage on. We conclude that our in vitro model can recapitulate DM1-specific mechanisms and opens doors to a deeper understanding of the fundamental mechanisms of humen disease.