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RNA sequencing of HSkM myotubes deficient in DMD, full-length dystrophin (DP427) and utrophin reveals common transcriptomic alterations

ABSTRACT: iRNA approaches were used to knock down the expression of dystrophin (DMD), including its full-length isoform DP427, and utrophin (UTRN) genes. Specifically, iRNA-mediated knockdown of both DMD (full-length dystrophin DP427) and UTRN was performed in HSkM myotubes. It is known that the shorter dystrophin isoform DP71 compensates for full-length dystrophin DP427 in the early stages of myofiber differentiation in cell models of Duchenne muscular dystrophy. Accordingly, DP427-deficient and DP71/DP427-deficient HSkM myotubes exhibit distinct changes in the expression of genes involved in membrane integrity and cytoskeletal functions. RNA-sequencing analyses revealed overlapping transcriptomic alterations in these HSkM cell lines, which corresponded to observed phenotypic abnormalities such as increased membrane permeability and intracellular calcium levels, mitochondrial aggregation, elevated reactive oxygen species (ROS), enhanced cyto- and genotoxicity, and induction of apoptosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303672 | GEO | 2026/01/27

REPOSITORIES: GEO

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	GSE303672_All_samples_raw_counts.csv.gz	Csv
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RNA sequencing of dystrophin- and utrophin-deficient HeLa cells reveals overlapping transcriptomic alterations

Project description:CRISPR/Cas9 and iRNA approaches were used to knock-out and knock-down expression of the dystrophin (DMD) and utrophin (UTRN) genes. RNA-sequencing analyses revealed overlapping transcriptomic alterations in HeLa cell lines relating to the observed phenotypic abnormalities, including increased membrane permeability and intracellular calcium levels, aggregation of mitochondria, elevated reactive oxygen species, increased cyto- and genotoxicity, and apoptosis.

2026-01-27 | GSE289357 | GEO

The effect of utrophin on the electrophysiological properties of DMD hiPSC-derived cardiomyocytes

Project description:DMD is a genetic disease, which leads to muscle weakness and cardiomyopathy. The latter remains incurable, being the main cause of death in DMD, therefore new therapeutic strategies are being sought to provide effective treatment. One of them considers upregulation of utrophin, a protein structurally and functionally homologous to dystrophin. In this study proteomic analysis of dystrophin-deficient and both dystrophin- and utrophin-deficient hiPSC-CM indicated on considerable differences in terms of contraction-related mechanisms. We thus investigated the role of utrophin in the maintenance of electrophysiological properties of DMD hiPSC-CM using the cells with additional utrophin deficiency and with utrophin upregulation. Obtained results indicated on disturbance of calcium handling in DMD hiPSC-CM, even more pronounced in DMD/UTRN KO hiPSC-CM and increased values of AHP in DMD hiPSC-CM. Utrophin upregulation improved both calcium oscillations and AHP values. Our findings highlight utrophin as important in the maintenance of the electrophysiological properties of DMD hiPSC-CM.

2024-06-20 | PXD044407 | Pride

Dystrophin-deficient and dystrophin and utrophin double-deficient mice crossed with mice with full-length hDMD genes

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Transcription profiling of mouse dystrophin-deficient and dystrophin and utrophin double-deficient animalse crossed with mice with full-length hDMD genes

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Microarray analysis of mdx mice expressing high levels of utrophin: therapeutic implications for DMD

Project description:Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disorder caused by dystrophin deficiency. Previous work suggested that increased expression of the dystrophin-related protein utrophin in the mdx mouse model of DMD can prevent dystrophic pathophysiology. Physiological tests showed that the transgenic mouse muscle functioned in a way similar to normal muscle. More recently, it has become possible to analyse disease pathways using microarrays, a sensitive method to evaluate the efficacy of a therapeutic approach. We thus examined the gene expression profile of mdx mouse muscle compared to normal mouse muscle and compared the data with that obtained from the transgenic line expressing utrophin. The data confirm that the expression of utrophin in the mdx mouse muscle results in a gene expression profile virtually identical to that seen for the normal mouse. This study confirms that a strategy to up-regulate utrophin is likely to be effective in preventing the disease. Keywords: Global gene expression profile

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Transcription profiling of mouse mdx animals expressing high levels of utrophin therapeutic implications for DMD

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The DMD locus harbours multiple long non-coding RNAs which orchestrate and control transcription of muscle dystrophin mRNA isoforms

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IPSC derived cardiac fibroblasts of DMD patients show compromised actin microfilaments, metabolic shift and pro-fibrotic phenotype.

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