Single cell transcriptomic analysis of skeletal muscle cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE247313 | GEO | 2023/11/23
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Skeletal muscle crucially depends on motor innervation, and, when damaged, on the resident muscle stem cells (MuSCs). However, the role and function of MuSCs in the context of denervation remains poorly understood. Methods: Alterations of MuSCs and their myofiber niche after denervation were investigated in a surgery-based mouse model of unilateral sciatic nerve transection. FACS-isolated MuSCs were subjected to RNA-sequencing and mass spectrometry for the analysis of intrinsic changes after denervation and in vivo assays, such as Cardiotoxin-induced muscle injury or MuSC transplantation, were performed to assess MuSC functions after denervation. Bioinformatic and histological analyses were conducted to further examine MuSCs and their myofiber niche after denervation. Results: Muscle cross section analysis revealed a significant increase in Pax7 (p-value= 0.0441), Pax7/Ki67 (p-value= 0.0023), MyoD (p-value= 0.0016) and Myog (p-value= 0.0057) positive cells after denervation, illustrating a break of quiescence and commitment to the myogenic lineage. An Omics approach showed profound intrinsic alterations on the mRNA (2613 differentially expressed genes, p-value <0.05) and protein (1096 differentially abundant proteins, q-value <0.05) level of MuSCs 21 days after denervation. Skeletal muscle injury together with denervation surgery caused deregulated regeneration, indicated by the reduced number of proliferating MuSCs and sustained high levels of developmental myosin heavy chain (Sham: 1 % vs DEN: 40 % of all myofibers), at 21 days post-surgery. In a transplantation assay, MuSCs from a denervated host were still able to engraft and fuse to form new myofibers, irrespective of the innervation status of the recipient muscle. Analysis of myofibers revealed not only massive changes in the expression profile (10492 differentially expressed genes, p-value <0.05) after denervation, but it was also shown that secretion of Opn and Tgfb1 from denervated myofibers was increased 30-fold and 6000-fold, respectively. Bioinformatic analyses indicated strong upregulation of gene expression of the transcription factor Junb in MuSCs from denervated muscles (log2 fold change = 3.27). Of interest, Tgfb1 recombinant protein was able to induce Junb gene expression in vitro, demonstrating that myofiber-secreted ligands can induce gene expression changes in MuSCs, which might result in the phenotypes observed after denervation. Conclusion: Skeletal muscle denervation is altering myofiber secretion, causing MuSC activation and profound intrinsic changes, leading to reduced regenerative capacity. As MuSCs possess a remarkable regenerative potential, they might represent a promising target for novel treatment options for neuromuscular disorders and peripheral nerve injuries.
2024-02-27 | PXD036993 | Pride
Project description:Fasting increases the level of skeletal muscle ATF4 mRNA, which promotes skeletal myofiber atrophy. To begin to determine the mechanism of ATF4-mediated myofiber atrophy, we compared the effects of fasting and ATF4 overexpression on global skeletal muscle mRNA expression in C57BL/6 mice.
2010-01-30 | GSE20103 | GEO
Project description:Fasting increases the level of skeletal muscle ATF4 mRNA, which promotes skeletal myofiber atrophy. To begin to determine the mechanism of ATF4-mediated myofiber atrophy, we compared the effects of fasting and ATF4 overexpression on global skeletal muscle mRNA expression in C57BL/6 mice.
2010-01-30 | GSE20101 | GEO
Project description:Overall, the widely disparate transcriptomes identified prior to RT among the three clusters support the notion that at least some of the inter-individual heterogeneity in propensity for RT-induced myofiber hypertrophy is likely pre-determined. Baseline comparisons of skeletal muscle transcript profiles from 44 subjects previously clustered (K-means cluster analysis) as non-, modest-, and extreme-responders (Non, n=15; Mod, n=14; Xtr, n=15) based on the magnitudes of change in vastus lateralis myofiber cross-sectional area (CSA) following 16-wk, 3-d/wk, high-intensity RT.
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Project description:The proper coordination of macrophages is essential for skeletal muscle repair. However, the full heterogenity of macrophages responding to injury has yet to be elucidated on the single-cell level. Furthermore, chronic inflammation may shift macrophage heterogeneity at steady-state and affect the generation of heterogeneity necessary for tissue repair. We use scRNA-sequencing to determine the heterogeneity of skeletal muscle macrophages during infection and wound repair (uninfected and infected). We identify multiple transcriptionally distinct macrophage subsets during injury in uninfected mice as well as during infection at steady-state. Interestingly, in response to injury, infected skeletal muscle macrophages fail to generate certain subsets of reparative macrophages in a timely fashion.
2018-10-04 | GSE113111 | GEO
Project description:Skeletal muscle is a heterogeneous tissue. Individual myofibers that make up the contractile muscle tissue exhibit variation in their metabolic and contractile properties. Although there are biochemical and histological assays to study myofiber heterogeneity, methods to analyze the transcriptomes of individual myofibers are lacking. We have developed single myofiber RNA-Seq (smfRNA-Seq) to analyze the whole transcriptome of an individual myofiber by combining single fiber isolation with Switching Mechanisms at 5’ end of RNA Template (SMART) technology. Our method provides high-resolution genome wide expression profiles of single myofibers. This method will be useful to study developmental and age-related dynamics in the composition of skeletal muscle.
2020-08-04 | GSE135364 | GEO
Project description:Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use global and tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells 3 to address this question. Deletion of miR-501 reduced myofiber size and resilience of muscle fibers to injury and exercise in adult skeletal muscle. miR-501 elicits this effect by changing sarcomeric gene expression in newly built myofibers in vivo.
2023-03-16 | GSE199111 | GEO
Project description:Myofibers (primary and secondary myofiber) are the basic structure of muscle and the determinant of muscle mass. To explore the skeletal muscle developmental processes from primary myofibers to secondary myofibers, we conducted an integrative 3D structure of genome and transcriptomic characterization of longissimus dorsi muscle (LDM) of pig from primary myofiber formation stage [embryonic day 35 (E35)] to secondary myofiber formation stage (E80). In the hierarchical genomic structure, we found that 11.43% of genome switched compartment A/B status, 14.53% of topologically associating domains (TADs) are changed intra- domain interactions (D-scores) and 3,166 genes with differential promoter-enhancer interactions (PEIs) and (or) enhancer activation from E35 to E80. The alterations of genome architecture were found to affect expression of genes that play significant roles in neuromuscular junction (NMJ) and embryonic morphogenesis in E35, such as NEFL, BRINP1, NTNG1, and MuSK and that function on skeletal muscle development or metabolism, typically MYL1, SLN, Sox6 and Mef2D.
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Project description:We performed transcriptional profiling to test the hypotheses that a) type I myofiber grouping severity in Parkinson's disease skeletal muscle is linked to distinct gene expression networks and b) high-intensity resistance exercise rehabilitation training influences the skeletal muscle transcriptome in individuals with Parkinson's disease.
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Project description:Following skeletal muscle injury (SMI), from post-injury reaction to repair consists of a complex series of dynamic changes.In this study, skeletal muscle tissue in rats was taken at 4h to 48h after injury for next-generation sequencing. We examined the transcriptional kinetics characteristics during above time periods after injury.
2021-07-08 | GSE171243 | GEO