Open AccessMyotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing
Author(s) -
Silvie Franck,
Edouard Couvreu de Deckersberg,
Jodi L. Bubenik,
Christina Markouli,
Lise Barbé,
Joke Allemeersch,
Pierre Hilven,
Geoffrey Duqué,
Maurice S. Swanson,
Alexander Gheldof,
Claudia Spits,
Karen Sermon
Publication year - 2022
Publication title -
biology open
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.936
H-Index - 41
ISSN - 2046-6390
DOI - 10.1242/bio.058978
Subject(s) - myogenesis , biology , myotonic dystrophy , myocyte , genetics , dna methylation , microbiology and biotechnology , skeletal muscle , rna splicing , muscular dystrophy , alternative splicing , cpg site , phenotype , cellular differentiation , gene , endocrinology , rna , gene expression , messenger rna
Skeletal muscle tissue is severely affected in myotonic dystrophy type 1 (DM1) patients, characterised by muscle weakness, myotonia and muscle immaturity in the most severe congenital form of the disease. Previously, it was not known at what stage during myogenesis the DM1 phenotype appears. In this study we differentiated healthy and DM1 human embryonic stem cells to myoblasts and myotubes and compared their differentiation potential using a comprehensive multi-omics approach. We found myogenesis in DM1 cells to be abnormal with altered myotube generation compared to healthy cells. We did not find differentially expressed genes between DM1 and non-DM1 cell lines within the same developmental stage. However, during differentiation we observed an aberrant inflammatory response and increased CpG methylation upstream of the CTG repeat at the myoblast level and RNA mis-splicing at the myotube stage. We show that early myogenesis modelled in hESC reiterates the early developmental manifestation of DM1.