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Gene regulation networks in muscle differentiation in lamin A associated muscular dystrophy
Author(s) -
Dutta Subarna
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08668
Subject(s) - muscular dystrophy , lamin , myogenesis , biology , myod , lmna , c2c12 , emerin , myocyte , mutant , genetics , microbiology and biotechnology , dysferlin , gene , nuclear protein , transcription factor
A type lamin has came into the limelight due to it’s involvement in the different plethora of diseases, collectively known as laminopathies. According to the previous reports, lamin A has involvement in disrupting differentiation of overexpressed R453W mutant of lamin A associated autosomal EDMD. In our immunofluorescence studies, we have ventured myoblast cells expressing a severe skeletal muscular dystrophy mutated lamin A, had a significant lower capacity to differentiate than wild type one. Anomalies in the reulations of protein expression levels of MyHC, MyoD were also checked by western blot analysis. These convey that, A type lamins play a crucial role by influencing expression of genes necessary for muscle cells differentiation .The abnormalities due to muscular dystrophy may lead to impairment of gene circuitry ,which are related to myoblast fusion necessary for the formation of mature myotubes. In our RNA sequencing study, we evaluated a thorogh gene expression profiling in the context of complex, highly coordinated process of muscle differentiation in stably transfection of wild type and mutant in C2C12 myoblast cells, which were differentiated for a specific time period. In the expression profiling of seven day time course, the genes which are showing highest scores in the disputes between wild type versus mutants ,were analysed further to get eloquent idea on cell signaling pathways were involved in. We identified dysfunctional pathways to compare wild type versus mutant of muscular dystrophy during differentiation of myoblast to myotube transition. These data provide a model in the muscular dystrophy pathogenesis to interlace the impacts of genetic modifiers in the differentiation potentiality. Support or Funding Information This work was funded by DAE, SERB‐DST.