Variations in gene expression among different types of human skeletal muscle
Ontology highlight
ABSTRACT: There is a consistent variation in the response of different skeletal muscle groups to mutations in genes known to cause muscular dystrophy, yet these muscles appear histologically similar. To better understand these phenotypic differences, we analyzed gene expression patterns in control muscle specimens obtained from four sites at autopsy: deltoid, quadriceps, gastrocnemius, and tibialis anterior (TA). A total of 35 muscle samples from nine individuals (four pediatric and five geriatric) were studied. Factors potentially influencing gene expression in the different samples included individuality, age, muscle type, gender, cause of death, postmortem interval, and ethnicity. The first three factors, in decreasing order, were found to have a significant impact on the stratification of muscle specimens. A novel analytic method, using a second round of normalization, was used to elicit differences between muscle types. This approach may be extended to a broader survey, potentially elucidating a molecular classification of the skeletal muscles. Keywords: anatomic comparison of different human skeletal muscles
Project description:There is a consistent variation in the response of different skeletal muscle groups to mutations in genes known to cause muscular dystrophy, yet these muscles appear histologically similar. To better understand these phenotypic differences, we analyzed gene expression patterns in control muscle specimens obtained from four sites at autopsy: deltoid, quadriceps, gastrocnemius, and tibialis anterior (TA). A total of 35 muscle samples from nine individuals (four pediatric and five geriatric) were studied. Factors potentially influencing gene expression in the different samples included individuality, age, muscle type, gender, cause of death, postmortem interval, and ethnicity. The first three factors, in decreasing order, were found to have a significant impact on the stratification of muscle specimens. A novel analytic method, using a second round of normalization, was used to elicit differences between muscle types. This approach may be extended to a broader survey, potentially elucidating a molecular classification of the skeletal muscles.
Project description:HIBM is a neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness. Here, gene expression was measured in muscle specimens from 10 HIBM patients carrying the M712T Persian Jewish founder mutation in GNE and presenting with mild histological changes, and from 10 healthy matched control individuals. Experiment Overall Design: Samples were taken from muscle specimens (deltoid, biceps, quadriceps, tibialis), from 10 HIBM patients carrying the M712T Persian Jewish founder mutation in GNE and presenting with mild histological changes. Ages of patients range between 20 to 59. Additional 10 matched samples were taken from healthy control individuals (deltoid, biceps, quadriceps, gluteus, paraspinally and triceps muscles), with age range 18 to 74.
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. In order to develop mRNA-based biomarkers of affected muscles, we used GeneChip Gene 1.0 ST arrays for global analysis of gene expression in muscle biopsy specimens obtained from FSHD subjects and their unaffected first degree relatives. FSHD typically affects biceps muscles more severely than deltoid muscles. To examine muscle-specific expression changes associated with FSHD while controlling for background genetic variation, we analyzed RNA extracted from both biceps and deltoids of FSHD subjects and unaffected first-degree relatives.
Project description:The aim of this study was to investigate the molecular mechanisms implicated in this mouse model of nemaline myopathy, and to further compare the molecular disease response in different skeletal muscles. For this purpose, snap frozen skeletla muscle specimens from wild type and transgenic for alpha tropomyosin slow mice were studied. Five different muscle types were used (diaphragm, plantaris, extensor digitorum longus, tibialis anterior, gastrocnemus). Mice were sacrificed between 7 and 10 months. RNA pools from 3-5 animals were created and each pool was hybridized to a U74Av2 Affymetrix GeneChip. Datasets from 36 GeneChips were included in this study. Experiment Overall Design: 36 skeletal mouse muscle RNA pools were used, from 5 different skeletal muscles, in two different conditions (wild type and transgenic)
Project description:Skeletal muscle regeneration is driven by the interaction of myogenic and non-myogenic cells. In aging, regeneration is impaired due to various dysfunctions of myogenic and non-myogenic cells, but this is not understood comprehensively. We collected an integrated atlas of 273,923 single-cell transcriptomes from muscles of young, old, and geriatric mice (4, 20, 26 months-old) at six time-points following myotoxin injury. We identified eight cell types, including T and NK cells and multiple macrophage subtypes that displayed accelerated or delayed dynamics between ages. Through pseudotime analysis, we observed myogenic cell states and trajectories specific to old and geriatric ages. To explain these age differences, we assessed cellular senescence by scoring experimentally derived and curated gene-lists, which pinpointed stalled senescent-like subsets specifically within the self-renewing muscle stem cells as elevated in older muscles. This resource provides a holistic portrait of the altered cellular states underlying skeletal muscle regeneration decline across mouse lifespan.
Project description:Skeletal muscle regeneration is driven by the interaction of myogenic and non-myogenic cells. In aging, regeneration is impaired due to dysfunctions of myogenic and non-myogenic cells, but this is not understood comprehensively. We collected an integrated atlas of 273,923 single-cell transcriptomes from muscles of young, old, and geriatric mice (~5, 20, 26 months-old) at six time-points following myotoxin injury. We identified eight cell types, including T and NK cells and macrophage subtypes, that displayed accelerated or delayed response dynamics between ages. Through pseudotime analysis, we observed myogenic cell states and trajectories specific to old and geriatric ages. To explain these age differences, we assessed cellular senescence by scoring experimentally derived and curated gene-lists. This pointed to an elevation of senescent-like subsets specifically within muscle stem cells in aged muscles in both single-cell and spatial transcriptomics datasets. This resource provides a holistic portrait of the altered cellular states underlying skeletal muscle regenerative decline across mouse lifespan.
Project description:Muscle stem cells (MuSCs) are required for muscle regeneration. In resting muscles, MuSCs are kept in quiescence. After injury, MuSCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. Age-associated impairments in stem cell functions correlate with a decline in somatic tissue regeneration capacity during aging. However, the mechanisms underlying the molecular regulation of adult stem cell aging remain elusive. Here, we obtained quisecent MuSCs from young, old, geriatric mice for high resolution mass spectrometry Bruker timsTOF Pro. By comparison of young proteome to old MuSCs proteome or geriatric MuSC proteome, we identified the pathways that are differentially during aging.
Project description:TLR4/NF-κB signaling plays a central mediator in response to danger signals released in the muscle ischemia-reperfusion injury (IRI). This study was designed to profile TLR4/NF-κB-responsive microRNAs (miRNAs) in the skeletal muscles following IRI. Following 2 h of ischemia and subsequent reperfusion for indicated times (0 h, 4 h, 1 d, and 7 d) of the isolated thigh skeletal muscles based on femoral artery perfusion of C57BL/6, Tlr4–/–, and NF-κB–/–mice, the muscle specimens were analyzed with an miRNA array to detect the TLR4/NF-κB-responsive miRNAs.
Project description:Soleus muscle has the most abundant H19 expression compared to other skeletal muscle tissues. In order to identify genes regulated by long noncoding RNA H19 in skeletal muscle, we performed RNA-Seq with dissected WT and H19KO soleus muscles from 21 week old mice. Among the differentially expressed genes, we found skeletal muscle - overexpressed gene DUSP27, which potentially plays an important role in regulating skeletal muscle glucose metabolisim by regulating the activitiy of AMPK, might be a target of H19 mediated regulation.
Project description:Oxidative posttranslational modifications (Ox-PTMs) regulate cellular homeostasis in several tissues, including skeletal and cardiac muscles. The putative relationship between Ox-PTMs and intrinsic components of oxidative energy metabolism has not been previously described. We determined the metabolic phenotype and the Ox-PTM profile in the skeletal and cardiac muscles of rats selected for low (LCR) or high (HCR) intrinsic aerobic capacity. The HCR rats have a pronounced increase in mitochondrial content and antioxidant capacity when compared to LCR rats in the skeletal muscle, but only modest changes in the cardiac muscle. Redox proteomics analysis reveals that HCR and LCR rats have different Ox-PTM of cysteine (Cys) residue profile in the skeletal and cardiac muscles. HCR rats have higher number of oxidized Cys residues in the skeletal muscle and conversely display higher number of reduced Cys residues in the cardiac muscle than LCR rats. Most of the proteins with differentially oxidized Cys residues in the skeletal muscle are important regulators of the oxidative metabolism. The most significantly oxidized protein in the skeletal muscle of HCR rats is malate dehydrogenase (MDH1). Interestingly, HCR rats show higher MDH1 activity in the skeletal muscle, but not in the cardiac muscle. Thus, this study uncovers an association between Ox-PTMs and intrinsic aerobic capacity, providing new insights into the role of Ox-PTMs as essential signaling to maintain metabolic homeostasis in different muscle types.