scholarly journals Skeletal Muscle Cell Growth Alters the Lipid Composition of Extracellular Vesicles

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 619
Author(s):  
Taylor R. Valentino ◽  
Blake D. Rule ◽  
C. Brooks Mobley ◽  
Mariana Nikolova-Karakashian ◽  
Ivan J. Vechetti
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Vesicles ◽  
Muscle Cell ◽  
Lipid Composition ◽  
Culture Media ◽  
Skeletal Muscle Cell ◽  
Bioactive Lipids ◽  
Hypertrophic Growth ◽  
Sphingosine 1 Phosphate ◽  
Lipid Chain

We sought to characterize the lipid profile of skeletal muscle cell-derived Extracellular Vesicles (EVs) to determine if a hypertrophic stimulus would affect the lipid composition of C2C12 myotube-derived EVs. Analyses included C2C12 murine myoblasts differentiated into myotubes and treated with Insulin-Like Growth Factor 1 (IGF-1) for 24 h to induce hypertrophic growth. EVs were isolated from cell culture media, quantified using Nanoparticle Tracking Analysis (NTA) and analyzed using Transmission Electron Microscopy (TEM). EVs were homogenized and lipids extracted for quantification by Mass Spectrometry followed by downstream lipid class enrichment and lipid chain analysis. IGF-1 treatment elicited an increase in CD63 and CD81 levels (39% and 21%) compared to the controls (16%), respectively. Analysis revealed that skeletal muscle-derived EVs are enriched in bioactive lipids that are likely selectively incorporated into EVs during hypertrophic growth. IGF-1 treatment of myotubes had a significant impact on the levels of diacylglycerol (DG) and ceramide (Cer) in secreted EVs. Specifically, the proportion of unsaturated DG was two- to three-fold higher in EVs derived from IGF-treated cells, as compared to those from control cells. The levels of saturated DG were unaffected. Selective increases were similarly seen in C16- and C24-Cer but not in other species. Levels of free sphingoid bases tended to decrease, while those of sphingosine-1-phosphate was unaffected. Our results suggest that the lipid composition and biogenesis of skeletal muscle-derived EVs, are specific and highly selective during hypertrophic growth.

THE MYOGRAM OF THE ISOLATED SKELETAL MUSCLE CELL

Science ◽  
1930 ◽  
Vol 72 (1853) ◽  
pp. 17-18 ◽  
Author(s):  
D. E. S. Brown ◽  
F. J. M. Sichel
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cell ◽  
Skeletal Muscle Cell

scholarly journals Human and rat skeletal muscle single-nuclei multi-omic integrative analyses nominate causal cell types, regulatory elements, and SNPs for complex traits

2021 ◽  
Author(s):  
Peter Orchard ◽  
Nandini Manickam ◽  
Christa Ventresca ◽  
Swarooparani Vadlamudi ◽  
Arushi Varshney ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Cell ◽  
Muscle Fiber ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Skeletal Muscle Cell ◽  
Rna Seq ◽  
Rat Skeletal Muscle ◽  
Integrative Analyses ◽  
Single Nucleus

Skeletal muscle accounts for the largest proportion of human body mass, on average, and is a key tissue in complex diseases and mobility. It is composed of several different cell and muscle fiber types. Here, we optimize single-nucleus ATAC-seq (snATAC-seq) to map skeletal muscle cell–specific chromatin accessibility landscapes in frozen human and rat samples, and single-nucleus RNA-seq (snRNA-seq) to map cell-specific transcriptomes in human. We additionally perform multi-omics profiling (gene expression and chromatin accessibility) on human and rat muscle samples. We capture type I and type II muscle fiber signatures, which are generally missed by existing single-cell RNA-seq methods. We perform cross-modality and cross-species integrative analyses on 33,862 nuclei and identify seven cell types ranging in abundance from 59.6% to 1.0% of all nuclei. We introduce a regression-based approach to infer cell types by comparing transcription start site–distal ATAC-seq peaks to reference enhancer maps and show consistency with RNA-based marker gene cell type assignments. We find heterogeneity in enrichment of genetic variants linked to complex phenotypes from the UK Biobank and diabetes genome-wide association studies in cell-specific ATAC-seq peaks, with the most striking enrichment patterns in muscle mesenchymal stem cells (∼3.5% of nuclei). Finally, we overlay these chromatin accessibility maps on GWAS data to nominate causal cell types, SNPs, transcription factor motifs, and target genes for type 2 diabetes signals. These chromatin accessibility profiles for human and rat skeletal muscle cell types are a useful resource for nominating causal GWAS SNPs and cell types.

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