Similar Datasets
Project description:FSHD and control immortalised myoblasts show repression of Pax7 target genes
2017-08-19 | GSE102812 | GEO
Project description:RNA-seq of FSHD and control immortalised myoblasts II
| PRJNA508799 | ENA
Project description:The gene expression pathways leading to muscle pathology in facioscapulohumeral dystrophy (FSHD) remain to be elucidated. This muscular dystrophy is caused by a contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2. We compared expression of control and FSHD myoblasts and myotubes (three preparations each) on exon microarrays (Affymetrix Human Exon 1.0 ST) and validated FSHD-specific differences for representative genes by qRT-PCR on additional myoblast cell strains. The FSHD and control myoblasts used for these experiments were shown to grow and differentiate into myotubes equally efficiently as control myoblasts. There were no significant FSHD-control differences in RNA levels for MYOD1 and MYOG at the myoblast and myotube stages and for MYF5 and MYF6 at the myoblast stage. In contrast, 295 other genes were dysregulated at least 2-fold in FSHD vs. control myoblasts (p <0.01, adjusted for multiple comparisons). Remarkably, only 10% of the FSHD-associated gene dysregulation at the myoblast stage was downregulation. At the myotube stage, about ten times as many genes exhibited FSHD-associated downregulated as at the myoblast stage and twice as many genes displayed FSHD-associated upregulation. The FSHD-related changes in RNA levels appear to be due to posttranscriptional as well as transcriptional alterations. Among the prominently dysregulated pathways were signaling and oxidative stress pathways. By comparing expression profiles of control myoblasts and myotubes to each other and to 19 non-muscle cell types profiled identically, our study also revealed many new myogenesis associations for genes not previously annotated as muscle-specific. Keywords: Disease state analysis and time course for differentiation
2011-09-29 | GSE26145 | GEO
Project description:Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight to disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; D2O) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from 2 individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4483 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample. FSHD myoblasts exhibited a greater abundance but slower turnover rate of subunits of mitochondrial respiratory complexes and mitochondrial ribosomal proteins, which may indicate an accumulation of ‘older’ less viable mitochondrial proteins in myoblasts from individuals affected by FSHD. Our results highlight the importance of post-transcriptional processes and protein turnover in FSHD pathology and provide a resource for the FSHD research community to explore this burgeoning aspect of FSHD.
2023-06-27 | PXD038818 | Pride
Project description:Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease characterized by progressive asymmetric muscle weakness. Myoblasts isolated from FSHD muscles exhibit morphological differentiation defects and show a distinct transcription profile. These abnormalities may be linked to the muscle weakness in FSHD patients. Here, we have tested whether fusion of FSHD myoblasts (obtained from 2 patients) with primary myoblasts isolated from 2 healthy individuals could correct the differentiation defects. Our results show that the number of hybrid myotubes with normal phenotype increased with the percentage of normal myoblasts initially cultured. We demonstrated that a minimum of 50% of normal nuclei is required for a phenotypic correction of the FSHD phenotype. To test the correction on the functional level we analyzed transcriptomic profiles of phenotypically corrected hybrid myotubes. These myotubes were cultured in DMEM with 10% FBS. The present study concerns gene expression of FSHD, normal and hybrid myotubes after RNA extraction (TriPrep NucleoSpin ® kit) according to manufacturer’s instructions. Gene expression was performed in single color on Agilent 8x60K Human whole genome (design 039494) minimum in duplicates in each condition. Transcriptomic profiles of phenotypically corrected hybrid myotubes showed that the expression of deregulated genes in FSHD myotubes became almost normal. We thus propose that while phenotypical and functional correction of FSHD is feasible, it requires more than 50% of normal myoblasts, it creates limitations for cell therapy in the FSHD context.
2015-08-17 | E-MTAB-3658 | biostudies-arrayexpress
Project description:RNAseq of FSHD and control LCLs and primary myoblasts with corresponding in vitro differentiated myotubes
2020-06-30 | GSE153523 | GEO
Project description:The specific gene(s) responsible for FSHD phenotype have not yet been identified. We used the Human GeneChip Exon 1.0 ST platform to analyze the global gene expression profiles of FSHD-1, FSHD-2 and controls during myogenic differentiation. In this dataset, we include the expression data of human primary myoblasts obtained from three FSHD-1 and two FSHD-2 patients, and three healthy controls (CN). This data are used to evaluate the molecular perturbation of FSHD upon muscle differentiation; we compared patients and CN proliferating myoblasts as well as the corresponding myotubes obtained after 8 days of cell differentiation. 16 expression profiles were generated from 6 different cell types: including myoblasts and myotubes from healthy donors and FSHD-1 and FSHD-2 patients. Gene probesets with P < 0.01 and FC > 2 were selected in FSHD-1 assay, whereas P < 0.001 and FC > 2 were used in FSHD-2, in the attempt to overcame problems due to the small sample size analyzed.
2011-07-07 | E-GEOD-26061 | biostudies-arrayexpress
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disease caused by expression of the transcription factor DUX4, which we previously found to be associated with plasma membrane (PM) repair deficits. However, the molecular mechanisms associated with poor membrane repair are not clear. Here, we show PM injury itself results in mild but significant increase in DUX4 mRNA expression, as well dysregulation of genes enriched in pathways critical for membrane repair. We find these dysregulated genes to be sensitive classifiers of FSHD status in human muscle biopsies, indicating their potential utility as novel biomarkers. In addition, FSHD myoblasts show dysregulation of genes in the ferroptosis cell death signaling pathway in response to membrane damage. Subsequent experiments indicated FSHD myoblasts present with hallmark features of ferroptotic stress, including elevated labile ferrous (Fe2+) iron, and lipid peroxidation at baseline and post-injury. Furthermore, we demonstrate that the expression of ferroptosis biomarkers is elevated in FSHD muscle biopsies, which is predictive of the presence of inflammation and positively correlates with the degree of fatty infiltration in FSHD skeletal muscle. Increasing labile iron and lipid peroxidation worsens membrane repair in FSHD myoblasts, while treatment with the iron chelator 2,2′-Bipyridyl and ferroptosis inhibitor ferrostatin-1 improve repair. These data are the first to identify signs of ferroptotic stress in FSHD myoblasts, and demonstrate the potential therapeutic benefit of iron chelation and ferroptosis inhibition to improve membrane repair capacity in FSHD.
2026-04-02 | GSE303359 | GEO
Project description:Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight to disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; D2O) labelling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from 2 individuals affected by FSHD and their unaffected siblings (UASb). Cells were treated with or without MOE to silence DUX4
2023-06-27 | PXD042374 | Pride
Project description:The specific gene(s) responsible for FSHD phenotype have not yet been identified. We used the Human GeneChip Exon 1.0 ST platform to analyze the global gene expression profiles of FSHD-1, FSHD-2 and controls during myogenic differentiation. In this dataset, we include the expression data of human primary myoblasts obtained from three FSHD-1 and two FSHD-2 patients, and three healthy controls (CN). This data are used to evaluate the molecular perturbation of FSHD upon muscle differentiation; we compared patients and CN proliferating myoblasts as well as the corresponding myotubes obtained after 8 days of cell differentiation.
2011-07-07 | GSE26061 | GEO