Transcriptomic analysis of cultured isogenic myotonic dystrophy type 1 myoblasts with and without the DMPK CTG repeat

RNA-seq on proliferating myoblasts of the DM11 line carrying 13 and 2600 CTG repeats in the DMPK gene, compared to their genome-edited counterparts without both the 13 and 2600 CTG repeat or just lacking the 2600 CTG repeat. Overall design: DM1 patient-derived and immortalized myoblasts (DM11) were genome-edited using CRISPR-Cas9 to excise the CTG repeat from the DMPK gene, thereby creating isogenic healthy controls for the DM1 cell line. After the CRISPR procedure, cells were clonally expanded and genetically characterized. We performed RNAseq on polyA selected RNA of one myoblast clone of which exclusively the expanded CTG repeat was excised (1E6), three clones of which the CTG repeat of both alleles was excised (3E3, 3B11 and 4A3) and three clones of which the repeat was still present after this procedure (4F9, EA11 and EA7), along with the DM11 source cell line (DM11 parental). This procedure and initial characterisation is described in Van Agtmaal et al. (2017) Molecular Therapy vol. 25 issue 1 p24-43