Myotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing
| Autor: | 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 D. Sermon |
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| Přispěvatelé: | Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Medicine and Pharmacy academic/administration, Reproduction and Genetics, Medical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
musculoskeletal diseases
Life Sciences & Biomedicine - Other Topics RNA mis-splicing EXPRESSION congenital hereditary and neonatal diseases and abnormalities INSTABILITY Muscle Development Myotonic dystrophy type I CTG REPEAT Methylation Myotonin-Protein Kinase General Biochemistry Genetics and Molecular Biology DISEASE Humans Myotonic Dystrophy Myogenic differentiation Muscle Skeletal Biology Embryonic Stem Cells Science & Technology Myotonic dystrophy type 1 Methods & Techniques DELETION PATHWAYS EXPANSION human embryonic stem cells GENE CpG methylation RNA Human embryonic stem cells General Agricultural and Biological Sciences Life Sciences & Biomedicine MUSCLE FUNCTION HUMAN ES |
| Zdroj: | Biology Open article-version (VoR) Version of Record |
| Popis: | 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. Summary: Early developmental abnormalities in myotonic dystrophy type 1 are reiterated in vitro in myotubes differentiated from human embryonic stem cells that carry the mutation. |
| Databáze: | OpenAIRE |
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