Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Aerobic training induces physiological and cellular benefits in myotonic dystrophy type 1 patients

ABSTRACT: Myotonic dystrophy type 1 (DM1) is a progressive life-limiting neuromuscular disorder with no available cure. In the current study, we examined the extent to which 12-weeks of cycle ergometry can recuperate clinical and physiological metrics in DM1 patients. Furthermore, we studied the underlying mechanisms through which exercise elicits benefits in skeletal muscle. DM1 was associated with impaired muscle function, fitness, lung capacity, and mitochondrial function. Exercise training induced several clinical, physical, and metabolic advantages in DM1 patients. We highlight that exercise-induced molecular and cellular alterations in patients do not conform with previously published data in murine models and propose an alternative mechanism. Lastly, we briefly outline the involvement of small nucleolar RNAs as a novel component within the DM1 pathophysiology. Taken together, our data supports the efficacy of aerobic training to mitigate the relentless progression of DM1 in individuals affected.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184951 | GEO | 2022/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Individual transcriptomic response to strength-training for myotonic dystrophy type 1 patients

Project description:Myotonic dystrophy type 1 (DM1), the most common form of adult-onset muscular dystrophy, is caused by a CTG expansion resulting in significant transcriptomic dysregulation that leads to muscle weakness and wasting. While strength training is clinically beneficial in DM1, molecular effects had not been studied. To determine whether training rescued transcriptomic defects, RNA-sequencing was performed on vastus lateralis samples from nine male DM1 patients before and after a 12-week strength training program and six male controls who did not undergo training. Differential gene expression and alternative splicing analysis were correlated with the one-repetition maximum strength evaluation method (leg extension, leg press, hip abduction, and squat). While training program-induced improvements in splicing were similar among most individuals, rescued splicing events varied considerably between individuals. Gene expression improvements were highly varied between individuals with the percentage of differentially expressed genes rescued after training strongly correlated with strength improvements. Evaluating transcriptome changes individually revealed responses to the training not evident from grouped analysis, likely due to disease heterogeneity and individual exercise response differences. Our analyses indicate that transcriptomic changes are associated with clinical outcomes in DM1 patients undergoing training and these changes are often specific to the individual and should be analyzed accordingly.

2023-03-26 | GSE208639 | GEO

RNA sequencing of skeletal muscle of myotonic dystrophic (DM1) patients

Project description:Introduction: Myotonic dystrophy of type 1 (DM1), the most common dystrophy in adults, is an autosomal dominant inherited disease, affecting around 1 in 8000 person. Patients suffering from DM1 develop essentially muscle disorders such as myotonia, muscle weakness, muscle loss and atrophy. The disease is caused by the mutation of the DMPK "Dystrophia Myotonica Protein Kinase" gene. The mutation correspond to an abnormally large expansion of CTG tri-nucleotides repeats located in the 3'-untranslated region of this gene. Expanded CTG repeats are normally transcribed, but accumulates in RNA aggregates that sequester RNA-binding proteins such as the splicing regulator MBNL1. Consequently, due to MBNL1 sequestration, DM1 is characterized by aberrant splicing of a wide number of mRNA, which are themselves responsible for the symptoms observed in the disease. Purpose: To determine as much as possible novel splicing misregulations taking place in DM1 skeletal muscle, we performed a paired-end RNA sequencing (RNA-seq) using muscles samples of normal individuals (CTRL, n=3) versus muscles of DM1 patients (DM1, n=3). The data was analyzed by a bioinformatical software, called MISO, in order to map the alternative splicing changes between normal and DM1 muscle. The aim of this study was to get a broad and precise view of the splicing changes occurring in DM1 muscle.

2017-08-24 | GSE85984 | GEO

Overexpression of the non-muscle RBFOX2 isoform triggers cardiac conduction defects in myotonic dystrophy

Project description:Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by a CTG trinucleotide repeat expansion in the 3′ untranslated region of DMPK gene. Heart dysfunctions occur in nearly 80% of DM1 patients and are the second leading cause of disease-related deaths, yet, the underlying mechanisms remain unclear. Herein, we report that upregulation of a non-muscle splice isoform of RNA binding protein RBFOX2 in DM1 heart tissue—due to altered splicing factor and microRNA activities—induces the characteristic cardiac conduction defects detected in DM1 individuals. Mice engineered to express the non-muscle RBFOX2 isoform in heart via tetracycline- inducible transgenesis, or CRISPR/Cas9 targeted genome editing, reproduced DM1- related cardiac-conduction delay and spontaneous episodes of arrhythmia. Furthermore, by integrating RNA binding with cardiac transcriptome datasets of DM1 patients, and mice expressing the non-muscle RBFOX2 isoform, we identified a core network of RBFOX2-driven splicing defects in sodium, potassium, and calcium channels that can alter their rate of ion diffusion and electrophysiological properties. Thus, our results uncover a trans-dominant role for an aberrantly expressed RBFOX2 isoform in DM1 cardiac pathogenesis.

2020-03-10 | GSE126771 | GEO

Expression data from Myotonic dystrophy type 1 (DM1) patient-derived induced pluripotent cell

Project description:DM1-iPSCs were generated from the peripheral blood of male adult patients. All clones were generated using episomal vectors. For skeletal muscle differentiation of the DM1-iPSCs, tet-on MYOD1 expression vector was transfected into DM1-iPSCs. To examine whether DM1-iPSC clones with different repeat sizes have acquired different characteristics, we isolated DM1-iPSC clones with different repeat sizes. We isolated 2 clones (S45 and S118) showing repeat size of 400~900, 2 clones (S14 and S24) showing repeat size of 1200~1600, and 2 clones (S1 and S16) showing repeat size of 1800~2800.

2024-12-16 | GSE214626 | GEO

Expression and Splicing Analysis of Myotonic Dystrophy and Other Dystrophic Muscle

Project description:The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype. In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls. For the exon array profiling on the Human Exon 1.0 ST array (Affymetrix Santa Clara, CA) we used a panel of 28 skeletal muscle biopsies from DM1 (n=8), DM2 (n=10), Becker muscular dystrophy, BMD, (n=3), Duchenne muscular dystrophy, DMD (n=1), Tibial muscular dystrophy, TMD, (n=2) and normal skeletal muscle (n=4). Normal control RNAs were purchased commercially. .CEL files were generated with a pre-commercial version of the Affymetrix processing software, and the headers might be non-standard. In our lab, users of the Partek software could use them, whereas users of GeneSpring had to modify the header information.

2016-01-05 | E-GEOD-48828 | biostudies-arrayexpress

Effects of exercise training on skeletal muscle insulin sensitivity in obesity patients undergoing RYGB surgery: a randomized controlled trial

Project description:We reported that skeletal muscle insulin sensitivity was restored to a lean phenotype with exercise training in patients undergoing RYGB surgery. For that, the goals of this study is to identify changes in the skeletal muscle transcriptome profiling (RNA-seq) that could explain the insulin sensitivity improvement of RYGB + exercise training group.

2020-05-19 | GSE137631 | GEO

Vastus lateralis biopsies from healthy and COPD patients before and after 3 weeks of endurance training

Project description:Study the effects of 3 weeks training exercise in chronic obstructive pulmonary disease (COPD) patients and healthy individuals. Skeletal muscle biopsies of 5 COPD patients (aged 63±2 year) and 3 age-matched healthy individuals were studied before and after 3 weeks of a supervised endurance training program. Samples were collected from open muscle biopsies of the vastus lateralis of 5 COPD patients and 3 age-matched healthy individuals before and after 3 weeks of a supervised endurance training program. Patients and controls underwent an endurance exercise program on a cycloergometer 5 days a week for three consecutive weeks. One 1 h session/day was established in all subjects, with effective exercise periods of at least 30 min in each case.

2014-09-01 | E-GEOD-27543 | biostudies-arrayexpress

Vastus lateralis biopsies from healthy and COPD patients before and after 8 weeks of exercise training

Project description:Study the training exercise effects in chronic obstructive pulmonary disease (COPD) patients and aged-matched healthy individuals. Skeletal muscle biopsies from 9 stable COPD patients with normal fat free mass index (FFMI, 21Kg/m2) (COPDN), 6 COPD patients with low FFMI (16Kg/m2) (COPL), and 12 healthy sedentary subjects (FFMI 21Kg/m2) before and after 8 weeks of a supervised endurance exercise program were analyzed. Samples were collected from open biopsies from the musculus vastus lateralis of COPD patients and healthy individuals before and after 8 weeks of exercise training. Constant-work rate exercise at 70% of pre-training Watts peak (Wpeak) (CardiO2 cycle Medical Graphics Corporation, USA) was carried out before and after 8 weeks of supervised interval training with a cycloergometer until pre-training endurance time exhaustion. Measurements before and after training were obtained at isowork-rate and iso-time.

2013-11-16 | E-GEOD-27536 | biostudies-arrayexpress

RNA sequencing of heart samples of myotonic dystrophic (DM1) patients

Project description:Analysis of alternative splicing in heart (left ventricles) samples of 3 adult DM1 patients versus 3 adult controls PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed by massive parrallel sequencing

2015-04-14 | E-GEOD-67812 | biostudies-arrayexpress

Exon array of heart samples of myotonic dystrophic patients

Project description:Analysis of alternative splicing of left ventricles heart samples of 3 DM1 adult versus 3 adult controls PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed on Exon Array (Affymetrix)

2016-01-21 | E-GEOD-67067 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data