Muscle from patients with mitochondrial myopathies and congenital muscular dystrophies versus normal human muscle
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Susana Kalko
PROVIDER: E-GEOD-43698 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Global gene expression analysis was performed comparing human skeletal muscle samples from patients with various forms of muscular dystrophy and mitochondrial myopathies in order to identify specific gene expression changes associated with collagen VI deficiency (leading to Ullrich´s Congenital Muscular Dystrophy) and depletion of mitochondrial DNA relative to other mitochondrial myopathies
2015-01-20 | GSE43698 | GEO
Project description:Summary: Genetic disorders of muscle cause muscular dystrophy, and are some of the most common inborn errors of metabolism. Muscle also rapidly remodels in response to training and innervation. Muscle weakness and wasting is important in such conditions as aging, critical care medicine, space flight, and diabetes. Finally, muscle can also be used to investigate systemic defects, and the compensatory mechansisms invoked by cells to overcome biochemical and genetic abnormalities. Here, we provide a 13 group data set for comparative profiling of human skeletal muscle. Groups studied are: Normal human skeletal muscle, Acute quadriplegic myopathy (AQM; critical care myopathy), Juvenile dermatomyositis (JDM), Amyotophic lateral sclerosis (ALS), spastic paraplegia (SPG4; spastin), Fascioscapulohumeral muscular dystrophy (FSHD), Emery Dreifuss muscular dystrophy (both X linked recessive emerin form; autosomal dominant Lamin A/C form), Becker muscular dystrophy (partial loss of dystrophin), Duchenne muscular dystrophy (complete loss of dystrophin), Calpain 3 (LGMD2A), dysferlin (LGMD2B), FKRP (glycosylation defect; homozygous for a missense mutation). U133A and U133B microarrays are both available. Hypothesis: This data set is able to define biochemical pathways that are either specific for a disease group, or shared between disease groups. For example, this data set has been used to determine the biochemical pathway perturbations that are shared between the two different types of Emery Dreifuss muscular dystrophy (lamin A/C, and emerin). Specific Aim: The specific aim of this study is to determine the disease-specific transcriptional profiles of these 13 patient groups, and to determine if these expression fingerprints provide either pathophysiology or diagnostic information for these diseases. Some of the groups in this large data set have been reported previously using U95A microarrays, as follows: Juvenile dermatomyositis (JDM): Tezak Z, Hoffman EP, Lutz JL, Fedczyna TO, Stephan D, Bremer EG, Krasnoselska-Riz I, Kumar A, Pachman LM. Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis. J Immunol. 2002 Apr 15;168(8):4154-63. PMID: 11937576 Duchenne muscular dystrophy (DMD) Chen YW, Zhao P, Borup R, Hoffman EP. Expression profiling in the muscular dystrophies: identification of novel aspects of molecular pathophysiology. J Cell Biol. 2000 Dec 11;151(6):1321-36. PMID: 11121445 Spastic paraplegia (SPG4, spastin): Molon A, Di Giovanni S, Chen YW, Clarkson PM, Angelini C, Pegoraro E, Hoffman EP. Large-scale disruption of microtubule pathways in morphologically normal human spastin muscle. Neurology. 2004 Apr 13;62(7):1097-104. PMID: 15079007 Acute quadriplegic myopathy (AQM): Di Giovanni S, Molon A, Broccolini A, Melcon G, Mirabella M, Hoffman EP, Servidei S. Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol. 2004 Feb;55(2):195-206. PMID: 14755723 Fascioscapulohumeral muscular dystrophy (FSHD): Winokur ST, Chen YW, Masny PS, Martin JH, Ehmsen JT, Tapscott SJ, van der Maarel SM, Hayashi Y, Flanigan KM. Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet. 2003 Nov 15;12(22):2895-907. Epub 2003 Sep 30. PMID: 14519683 Keywords: muscle disease comparison Groups studied are: Normal human skeletal muscle, Acute quadriplegic myopathy (AQM; critical care myopathy), Juvenile dermatomyositis (JDM), Amyotophic lateral sclerosis (ALS), spastic paraplegia (SPG4; spastin), Fascioscapulohumeral muscular dystrophy (FSHD), Emery Dreifuss muscular dystrophy (both X linked recessive emerin form; autosomal dominant Lamin A/C form), Becker muscular dystrophy (partial loss of dystrophin), Duchenne muscular dystrophy (complete loss of dystrophin), Calpain 3 (LGMD2A), dysferlin (LGMD2B), FKRP (glycosylation defect; homozygous for a missense mutation).
2005-10-14 | E-GEOD-3307 | biostudies-arrayexpress
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
Project description:Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. In this project, proteomics data from skeletal muscle of a genetically engineered DMD pig model were investigated in order to confirm muscular fibrosis and MSOT signals.
2020-01-09 | PXD016003 | Pride
Project description:Fibrosis and fat replacement in the skeletal muscle is a major complication that leads to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, our current knowledge on the in vivo properties of adipogenic stem and precursor cells remains unclear, mainly due to the high cell heterogeneity in skeletal muscles. For this purpose, we used single-cell RNA-sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identified a CD142 (F3) positive cell subpopulation in mice and humans that is responsible for the inhibition of adipogenesis. Furthermore, we found a completely altered composition of interstitial cells in muscular dystrophy, with a near absence of the CD142-positive cells. The novel discovery of these adipo-regulatory cells in the skeletal muscle aids our understanding regarding the aberrant fat deposition in muscular dystrophy, paving the way for treatments that potentially sustain ambulation in patients with muscular dystrophy.
2020-04-02 | GSE147883 | GEO
Project description:The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
2007-10-10 | E-GEOD-471 | biostudies-arrayexpress
Project description:Transgenic overexpression of Galgt2 in the skeletal muscles of mdx mice inhibits the development of disease pathology associated with muscular dystrophy. This is the case both in transgenic mice, where Galgt2 overexpression occurs from embryonic timepoints onward and in mdx mice where Galgt2 is overexpressed in the early postnatal period using Adeno-associated virus (AAV). Here, we use gene expression profiling to compare transcriptional changes resulting from embryonic and postnatal Galgt2 overexpression in mdx skeletal muscle. A surprising number of changes were in genes known to ameliorate muscular dystrophy when overexpressed (agrin, integrin alpha 7, ADAM12, Bcl2) or to cause muscular dystrophy when mutated (collagen VI (alpha1,alpha2), plectin 1, dystroglycan, selenoprotein N1, integrin alpha7, biglycan, dysferlin). Several genes involved in calcium homeostasis were also changed. In Galgt2 transgenic mice, where embryonic overexpression of Galgt2 in skeletal muscles alters neuromuscular development and muscle growth, the number of gene expression changes was vastly greater, however, 14% of genes altered in postnatal AAV-Galgt2 infected mdx muscles were also changed with embryonic overexpression. These experiments suggest that postnatal overexpression of Galgt2 inhibits muscular dystrophy in mdx mice via induction of a group of genes that, in aggregate, can govern membrane stability, membrane repair, calcium homeostasis, and apoptosis. Transgenic overexpression of Galgt2 in the skeletal muscles of mdx mice inhibits the development of disease pathology associated with muscular dystrophy. This is the case both in transgenic mice, where Galgt2 overexpression occurs from embryonic timepoints onward and in mdx mice where Galgt2 is overexpressed in the early postnatal period using Adeno-associated virus (AAV). Here, we use gene expression profiling to compare transcriptional changes resulting from embryonic and postnatal Galgt2 overexpression in mdx skeletal muscle. A surprising number of changes were in genes known to ameliorate muscular dystrophy when overexpressed (agrin, integrin alpha7, ADAM12, Bcl2) or to cause muscular dystrophy when mutated (collagen VI (alpha1,alpha2), plectin 1, dystroglycan, selenoprotein N1, integrin alpha7, biglycan, dysferlin). Several genes involved in calcium homeostasis were also changed. In Galgt2 transgenic mice, where embryonic overexpression of Galgt2 in skeletal muscles alters neuromuscular development and muscle growth, the number of gene expression changes was vastly greater, however, 14% of genes altered in postnatal AAV-Galgt2 infected mdx muscles were also changed with embryonic overexpression. These experiments suggest that postnatal overexpression of Galgt2 inhibits muscular dystrophy in mdx mice via induction of a group of genes that, in aggregate, can govern membrane stability, membrane repair, calcium homeostasis, and apoptosis. Experiment Overall Design: Microarrays were done in three groups at a time. 1) Transgenic Overexpression of Galgt2 - comprised to Wild Type (WT), Galgt2 Transgenic (CT), Dystrophin-Deficient (mdx), and Galgt2 Transgenic and Dystrophin-Deficient (CTmdx) each in duplicate 2) AAV-Mediated Galgt2 Gene Delivery in to the mdx gastrocnemius muscle in the postnatal period - comprised of AAVGalgt2 and PBS each in duplicate, and 3) Myoblasts and myotubes - comptised of one sample each of C1C12 myoblasts and myotubes, C2C12 myoblasts and myotubes stably transfected with Galgt2
2009-03-07 | E-GEOD-7863 | biostudies-arrayexpress
Project description:Molecular profiles of dystophin-deficient patients and normal human skeletal muscles on Affymetrix HG-U95A arrays Keywords = DMD Keywords = Duchenne muscular dystrophy Keywords = dystrophin Keywords = Affymetrix U95A array Keywords = skeletal muscle Keywords = gene expression profiles Keywords: other
2004-01-29 | E-GEOD-1004 | biostudies-arrayexpress
Project description:<p>The samples are drawn from a collection of patients with a heterogeneous set of neuromuscular disorders, including congenital muscular dystrophy, congenital myopathy, limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, and arthrogryposis, along with unaffected parents and siblings in some cases. The samples were collected by the following clinicians affiliated with the associated institutes: <ol> <li>Kathryn North and Nigel Clarke (Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, Australia)</li> <li>Hanns Lochmuller and Kate Bushby (The Newcastle Muscle Centre, Newcastle University, UK)</li> <li>Peter Kang (Boston Children's Hospital)</li> <li>Carsten Bonnemann (National Institutes of Health, Bethesda, MD, USA)</li> <li>Nigel Laing (University of Western Australia)</li> </ol> </p> <p> All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Agilent SureSelect Human All Exon Kit v2 or Illumina's Rapid Capture Exome enrichment kit and sequencing was performed on an Illumina HiSeq 2000. In addition some samples were whole genome sequenced on Illumina HiSeq X Ten.</p>
| phs000655 | dbGaP
Project description:Duchenne muscular dystrophy (DMD) is caused by genetic deficiency of dystrophin and characterized by massive structural and functional changes of skeletal muscle tissue, leading to terminal muscle failure. In this project, proteomics data from skeletal muscle of a genetically engineered DMD pig model treated by somatic gene editing are shown.
2020-02-05 | PXD014893 | Pride