Integrated fibre-specific methylome and proteome profiling of human skeletal muscle across males and females with fibre-type deconvolution.

IF 4.4 2区医学 Q2 CELL BIOLOGY

Skeletal Muscle Pub Date : 2025-10-10 DOI:10.1186/s13395-025-00396-0

Andrew S Palmer, Esther García-Domínguez, Megan F Taylor, Andrew Garnham, Kirsten Seale, Joel R Steele, Han-Chung Lee, Ralf B Schittenhelm, Nir Eynon

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引用次数: 0

Abstract

Background: Skeletal muscle is an important organ for health and movement, largely driven by specific muscle fibres. However, the comparison of fibre-type-specific DNA methylation and protein abundance from the same sample presents challenges. By combining previous methodological approaches we were able to directly compare the methylome and proteome in Type I and Type II human skeletal muscle fibres in males and females.

Methods: We assessed the methylome using the EPICv2 Infinium array and the proteome using liquid chromatography tandem mass spectrometry (LC-MS/MS) from Type I and Type II fibre pools from both males ( $n = 7$ ) and females ( $n = 5$ ).

Results: We identified 5,689 robust differentially methylated regions (Fisher P-value $< 0.001$ ) and found strong relationships between methylation and protein abundance in key contractile and metabolic genes. Further, we generated a reference matrix of Type I and Type II fibres and leveraged deconvolution algorithms to accurately estimate fibre-type proportions using whole-muscle DNA methylation data, providing a method to correct for fibre-type in future studies. These results are presented primarily as a resource for others to utilise.

Conclusion: We provide integrated methylome and proteome profiles of human muscle fibre-types generalisable to both male and females as a freely accessible interactive repository, MyoMETH ( https://myometh.net ), allowing further investigation into fibre regulation. Data are available via ProteomeXchange with identifier PXD066393 and the Gene Expression Omnibus at GSE304045 .

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综合纤维特异性甲基组和蛋白质组分析跨越男性和女性的人类骨骼肌纤维型反褶积。

背景：骨骼肌是健康和运动的重要器官，主要由特定的肌肉纤维驱动。然而，纤维类型特异性DNA甲基化和蛋白质丰度的比较来自同一样品提出了挑战。通过结合以前的方法，我们能够直接比较男性和女性I型和II型人类骨骼肌纤维中的甲基组和蛋白质组。方法：我们使用EPICv2 Infinium阵列评估甲基组，使用液相色谱串联质谱（LC-MS/MS）评估来自男性（n = 7）和女性（n = 5）的I型和II型纤维池的蛋白质组。结果：我们确定了5,689个差异甲基化区域（Fisher p值0.001），并发现甲基化与关键收缩和代谢基因的蛋白质丰度之间存在密切关系。此外，我们生成了I型和II型纤维的参考矩阵，并利用反卷积算法使用全肌肉DNA甲基化数据准确估计纤维类型比例，为未来研究中校正纤维类型提供了一种方法。这些结果主要是作为资源供他人利用。结论：我们提供了一个可自由访问的交互式存储库MyoMETH (https://myometh.net)，提供了适用于男性和女性的人类肌肉纤维类型的集成甲基组和蛋白质组图谱，允许进一步研究纤维调节。数据可通过ProteomeXchange（编号PXD066393）和Gene Expression Omnibus（编号GSE304045）获得。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Skeletal Muscle CELL BIOLOGY-

CiteScore

9.10

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators. Main areas of interest include: -differentiation of skeletal muscle- atrophy and hypertrophy of skeletal muscle- aging of skeletal muscle- regeneration and degeneration of skeletal muscle- biology of satellite and satellite-like cells- dystrophic degeneration of skeletal muscle- energy and glucose homeostasis in skeletal muscle- non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies- maintenance of neuromuscular junctions- roles of ryanodine receptors and calcium signaling in skeletal muscle- roles of nuclear receptors in skeletal muscle- roles of GPCRs and GPCR signaling in skeletal muscle- other relevant aspects of skeletal muscle biology. In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission. Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.