DNA methylation assessment from human slow- and fast-twitch skeletal muscle fibers

Begue, Gwénaëlle; Raue, Ulrika; Jemioło, Bożena; Trappe, Scott

doi:10.1152/japplphysiol.00867.2016

Cited by 52 publications

(39 citation statements)

References 91 publications

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“…Given that one of the major drivers of DNA methylation pattern is cell type, it could be that the altered methylation pattern in the superaged muscle reflects a change in the composition of muscle fiber types with age. We only know that the human type 1 slow‐twitch and type 2a fast‐twitch muscle fibers had similar levels and distributions of methylated CpGs at promoters and CGIs (Begue, Raue, Jemiolo, & Trappe, ). However, there is no information about whether the different muscle fibers undergo unique methylation changes in their own pattern with age.…”

Section: Discussionmentioning

confidence: 99%

Demethylation and derepression of genomic retroelements in the skeletal muscles of aged mice

2019

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Changes in DNA methylation influence the aging process and contribute to aging phenotypes, but few studies have been conducted on DNA methylation changes in conjunction with skeletal muscle aging. We explored the DNA methylation changes in a variety of retroelement families throughout aging (at 2, 20, and 28 months of age) in murine skeletal muscles by methyl‐binding domain sequencing (MBD‐seq). The two following contrasting patterns were observed among the members of each repeat family in superaged mice: (a) hypermethylation in weakly methylated retroelement copies and (b) hypomethylation in copies with relatively stronger methylation levels, representing a pattern of “regression toward the mean” within a single retroelement family. Interestingly, these patterns depended on the sizes of the copies. While the majority of the elements showed a slight increase in methylation, the larger copies (>5 kb) displayed evident demethylation. All these changes were not observed in T cells. RNA sequencing revealed a global derepression of retroelements during the late phase of aging (between 20 and 28 months of age), which temporally coincided with retroelement demethylation. Following this methylation drift trend of “regression toward the mean,” aging tended to progressively lose the preexisting methylation differences and local patterns in the genomic regions that had been elaborately established during the early period of development.

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Section: Discussionmentioning

confidence: 99%

Demethylation and derepression of genomic retroelements in the skeletal muscles of aged mice

2019

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“…Eighteen fiber-type specific samples were generated as previously described 20 . Briefly, all samples were prepared according to the following steps: (1) manual muscle fiber isolation, (2) muscle fiber clipping to allow for fiber-type identification via SDS-PAGE 6 , (3) muscle fiber pooling of alike fiber-types, (4) RNA extraction (TRI Reagent, Molecular Research Center, Cincinnati, OH) and RNA quantification (Quant-iT RNA assay kit, Invitrogen, Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

“…While this study was able to determine several muscle type specific genes, it is unclear whether these genes are truly fiber type specific or simply differ between muscle locations. Previous transcriptome studies of manually dissected fiber-types analyzed mouse skeletal muscle 18,19 or did not focus on human baseline transcriptome differences 8,20 . Isolated human skeletal muscle mononuclear cell populations (satellite cells, FAPs, etc.)…”

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confidence: 99%

Single-cell transcriptional profiles in human skeletal muscle

Rubenstein

Smith

Raue

et al. 2020

Sci Rep

Self Cite

234

225

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Skeletal muscle is a heterogeneous tissue comprised of muscle fiber and mononuclear cell types that, in addition to movement, influences immunity, metabolism and cognition. We investigated the gene expression patterns of skeletal muscle cells using RNA-seq of subtype-pooled single human muscle fibers and single cell RNA-seq of mononuclear cells from human vastus lateralis, mouse quadriceps, and mouse diaphragm. We identified 11 human skeletal muscle mononuclear cell types, including two fibro-adipogenic progenitor (FAP) cell subtypes. The human FBN1+ FAP cell subtype is novel and a corresponding FBN1+ FAP cell type was also found in single cell RNA-seq analysis in mouse. Transcriptome exercise studies using bulk tissue analysis do not resolve changes in individual cell-type proportion or gene expression. The cell-type gene signatures provide the means to use computational methods to identify cell-type level changes in bulk studies. As an example, we analyzed public transcriptome data from an exercise training study and revealed significant changes in specific mononuclear cell-type proportions related to age, sex, acute exercise and training. Our single-cell expression map of skeletal muscle cell types will further the understanding of the diverse effects of exercise and the pathophysiology of muscle disease.Skeletal muscle is a complex heterogeneous tissue consisting of multinucleated muscle fibers, immune cells, endothelial cells, muscle stem cells (satellite cells), non-myogenic mesenchymal progenitors (e.g., fibro-adipogenic progenitors, or FAPs), and other mononuclear cells 1 . To improve the understanding of skeletal muscle cell types and their transcriptional signatures, we studied human and mouse skeletal muscle mononuclear cells by single-cell RNA-sequencing and single human muscle fiber subtypes by RNA-seq.The majority of skeletal muscle is composed of the multinucleated fibers that facilitate movement. These muscle fibers include several fiber types of differing metabolic and functional properties 2-4 . While slow-twitch (or Type I) muscle fibers possess high oxidative capacity, fast-twitch (or Type II) muscle fibers have a high glycolytic capacity and are capable of supplying more power than Type I fibers 2-4 . Fiber-type composition differs across individuals and can change by as much as 10-30% during exercise training regimens 5-7 . Furthermore, the transcriptomic response to physical activity is different in each fiber-type as each fiber-type responds differently to different modes of exercise 8,9 . Crucially, muscle fibers secrete myokines, which both act locally within muscle tissue as well as influence other organs and tissues via hormone-like signaling 10 . Myokines may be responsible for the immune-, metabolism-, and cognition-related benefits of physical activity, as well as the chronic diseases that are caused by lack of physical activity (insulin resistance, cardiovascular disease, etc.) 10 .Besides multinucleated fibers, skeletal muscle contains many mononuclear cells, such as immune cells,...

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“…SkM differentiation, homeostasis, and reprogramming, such as fiber-type switching, relies on SkM-specific regulation of gene expression through SkM lineage-associated TFs, cell signaling, and epigenetics [7-12]. The TF drivers of myogenic differentiation are the four myogenic regulatory TFs encoded by MYOD1, MYF5, MYF6 , and MYOG , whose expression is cell type-specific and regulated by promoters, enhancers and DNA hypomethylation [13-16].…”

Section: Introductionmentioning

confidence: 99%

Epigenetics of skeletal muscle-associated genes in theASB, LRRC, TMEM, andOSBPLgene families

Ehrlich¹,

Lacey

Ehrlich

2019

Preprint

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Much remains to be discovered about the intersection of tissue-specific transcription control and the epigenetics of skeletal muscle (SkM), a very complex and dynamic organ. From four gene families, ASB, LRRC, TMEM, and OSBPL, we chose 21 genes that are preferentially expressed in human SkM relative to 52 other tissue types and analyzed relationships between their tissue-specific epigenetics and expression. We also compared their genetics, proteomics, and descriptions in the literature. For this study, we identified genes with little or no previous descriptions of SkM functionality (ASB4, ASB8, ASB10, ASB12, ASB16, LRRC14B, LRRC20, LRRC30, TMEM52, TMEM233, OSBPL6/ORP6, and OSBPL11/ORP11) and included genes whose SkM functions had been previously addressed (ASB2, ASB5, ASB11, ASB15, LRRC2, LRRC38, LRRC39, TMEM38A/TRIC-A, and TMEM38B/TRIC-B). Among the transcription-related SkM epigenetic features that we identified were super-enhancers, promoter DNA hypomethylation, lengthening of constitutive low-methylated promoter regions, and SkM-related enhancers for one gene embedded in a neighboring gene (e.g., ASB8-PFKM, LRRC39-DBT, and LRRC14B-PLEKHG4B gene-pairs). In addition, highly or lowly co-expressed long non-coding RNA (lncRNA) genes probably regulate several of these genes. Our findings give insights into tissue-specific epigenetic patterns and functionality of related genes in a gene family and can elucidate normal and disease-related regulation of gene expression in SkM.

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DNA methylation assessment from human slow- and fast-twitch skeletal muscle fibers

Cited by 52 publications

References 91 publications

Demethylation and derepression of genomic retroelements in the skeletal muscles of aged mice

Demethylation and derepression of genomic retroelements in the skeletal muscles of aged mice

Single-cell transcriptional profiles in human skeletal muscle

Epigenetics of skeletal muscle-associated genes in theASB, LRRC, TMEM, andOSBPLgene families

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