Genome studies of chromatin accessibility and gene expression during iPSC skeletal muscle induction and differentiation
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common genetic disease of skeletal muscles. Patients would have progressive muscle weakness and atrohpy of skeletal muscles. However, until now, no approved therapies exist specifically for FSHD. Recently, scientists developed an efficient and highly scalable monolayer system to differentiate human pluripotent stem cells (iPS) into skeletal muscles. Here, we exploited ATAC-Seq technology to explore changes in chromatin accessibility and transcription factor representation in open chromatin during the stepwise induction of healthy iPS, first into skeletal muscle progenitor cells (stage S1), and then into skeletal muscle myoblasts (stages S2). On the other hand, we used ISO-Seq dataset to characterize the stage-specific RNA expression correlated with specific stages in ATAC-Seq, differentially expressed genes and gene ontology and pathway analysis during iPS induction and the other five later stages of myogenesis. The study on open chromatin domains, transcription facors and RNA expression would help us to understand the mechanism behind skeletal muscle formation and to explore the effective treatment for FSHD.
Prof Charles P Emerson, UMMS