Omics datasets

We report extensive transcriptome and miRNome alterations in muscle cells derived from patients with LGMDD2 compared to healthy controls. Using a CRISPR/Cas9-mediated gene editing approach, we demonstrate partial recovery of gene expression and miRNA profiles in corrected cells. Transcriptomic analysis identified 2,508 differentially expressed genes (15% of the transcriptome) in patient-derived cells, with 44% of these changes significantly restored toward normal levels upon genetic correction. Similarly, miRNA analysis revealed that 28% of miRNAs were differentially expressed in the disease cells, and approximately 49% of these were recovered post-editing. The raw data from these analyses, including RNA sequencing (RNA-seq) and small RNA sequencing, are available in GEO under accession number GSE198551. These datasets offer valuable insights into the molecular mechanisms underlying LGMDD2 and the therapeutic potential of CRISPR/Cas9-mediated interventions.

This is a comprehensive analysis of transcriptome alterations in patient-derived myotubes treated with antagomiR-218 (aka antimiR-218), an antisense oligonucleotide targeting miR-218. The study used differentiated myotubes derived from immortalized fibroblasts of Myotonic Dystrophy (DM1) patients. Differentiation was induced by transdifferentiation with MyoD, and cells were maintained for 4 days under differentiation conditions before RNA extraction. The dataset highlights the deregulation and partial rescue of genes implicated in DM1 pathogenesis, offering insights into the molecular impact of miR-218 inhibition. Differential gene expression analysis revealed that antagomiR-218 restored up to 34% of the transcriptomic changes observed in DM1 cells, emphasizing its potential to ameliorate disease-associated molecular defects. Raw data for this study are publicly available in GEO under accession number GSE158216. This dataset represents a valuable resource for understanding the therapeutic mechanisms of miR-218 targeting in DM1.

The study focuses on transcriptomic analysis to explore the therapeutic potential of chloroquine (CQ) in treating myotonic dystrophy type 1 (DM1), a neuromuscular disorder caused by CTG trinucleotide repeat expansions in the DMPK gene. The expanded repeats sequester RNA-binding proteins, the Muscleblind-like (MBNL) proteins, leading to splicing defects. We demonstrated that CQ restores MBNL protein levels across Drosophila, mouse models, and patient-derived myoblasts. This upregulation improved molecular and physiological phenotypes, such as splicing regulation, muscle strength, and myotonia. RNA-sequencing data revealed significant recovery of disease-related genes post-CQ treatment, validating its role in mitigating splicing abnormalities and functional deficits. The GEO accession number for the dataset used in the study is GSE128844. These findings highlight CQ's potential as a novel therapeutic strategy for DM1, emphasizing the criticality of targeting MBNL depletion.

This study explores transcriptome datasets from patient-derived cells and Myotonic Dystrophy type 1 (DM1) muscle biopsies (www.DMSeq.org), and murine models to evaluate the therapeutic potential of blockmiRs in DM1. Using immortalized fibroblasts transdifferentiated into myotubes, 3D mouse muscle tissues, and HSALR mice, we demonstrated that blockmiRs targeting miRNAs involved in DM1 effectively restore splicing and gene expression. RNA-seq analysis revealed increased MBNL1 transcripts and proteins, along with rescued splicing of key genes like SORBS1 and MLH3. In vivo, blockmiRs improved muscle strength and reduced pathological features in HSALR mice, highlighting their therapeutic promise for DM1. The transcriptomic dataset used in this study is available under GEO accession number GSE173359.

The biological model employed in the RNA sequencing study consists of primary myoblasts derived from patients with myotonic dystrophy type 1 (DM1), a neuromuscular disease caused by CTG repeat expansions in the DMPK gene. Myoblasts were differentiated into myotubes and treated with chemically modified antimiRs targeting miR-23b and miR-218, which are natural repressors of MBNL1, a key splicing regulator depleted in DM1. RNA-seq analysis revealed 109 dysregulated genes in untreated DM1 cells compared to controls, with 69% of these gene expression abnormalities corrected upon antimiR treatment. Key findings include the reduction of DMPK transcripts and ribonuclear foci, enhanced MBNL1 protein levels, and the restoration of splicing patterns in DM1-associated genes. These results support antimiRs as promising therapeutic candidates for DM1. Primary datasets can be located under reference number GSE237411.​