Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism
Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism
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DOI：
10.1152/ajpcell.00540.2019
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发表时间：
2020-03-01
影响因子：
5.5
通讯作者：
Pillon, Nicolas J.
中科院分区：
文献类型：
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作者：
Abdelmoez, Ahmed M.;Puig, Laura Sardon;Pillon, Nicolas J.
大鼠 L6、小鼠 C2C12 和原代人骨骼肌细胞 (HSMC) 通常用于研究骨骼肌的生物过程，并且这些模型的实验数据非常丰富。然而，一致匹配的实验数据很少，不同细胞类型和成体组织之间的比较也存在问题。我们假设这些细胞模型之间的代谢差异可能反映在 mRNA 水平上。使用公开数据集来分析肌管和骨骼肌组织中的 mRNA 水平。评估 L6、C2C12 和 HSMC 肌管的增殖、葡萄糖摄取、糖原合成、线粒体活性和底物氧化以及对体外收缩的反应。转录组分析显示，编码肌动蛋白和肌球蛋白的基因 mRNA 在 C2C12 中富集，而 L6 肌管中编码葡萄糖转运蛋白和线粒体电子传递链的 5 个复合体的基因水平最高。一致的是，L6 肌管中胰岛素刺激的葡萄糖摄取和氧化能力最强。胰岛素诱导的糖原合成在 HSMC 中最高，但 C2C12 肌管的基线葡萄糖氧化水平较高。所有模型都对电脉冲刺激诱导的葡萄糖摄取和基因表达做出反应，但方式略有不同。我们的分析揭示了 L6、C2C12 或原代人类肌管的转录组和代谢谱存在很大程度的异质性。基于这些独特的特征，我们根据科学假设和生物学相关性，为正确使用这些模型提供建议。
Rat L6, mouse C2C12, and primary human skeletal muscle cells (HSMCs) are commonly used to study biological processes in skeletal muscle, and experimental data on these models are abundant. However, consistently matched experimental data are scarce, and comparisons between the different cell types and adult tissue are problematic. We hypothesized that metabolic differences between these cellular models may be reflected at the mRNA level. Publicly available data sets were used to profile mRNA levels in myotubes and skeletal muscle tissues. L6, C2C12, and HSMC myotubes were assessed for proliferation, glucose uptake, glycogen synthesis, mitochondrial activity, and substrate oxidation, as well as the response to in vitro contraction. Transcriptomic profiling revealed that mRNA of genes coding for actin and myosin was enriched in C2C12, whereas L6 myotubes had the highest levels of genes encoding glucose transporters and the five complexes of the mitochondrial electron transport chain. Consistently, insulin-stimulated glucose uptake and oxidative capacity were greatest in L6 myotubes. Insulin-induced glycogen synthesis was highest in HSMCs, but C2C12 myotubes had higher baseline glucose oxidation. All models responded to electrical pulse stimulation-induced glucose uptake and gene expression but in a slightly different manner. Our analysis reveals a great degree of heterogeneity in the transcriptomic and metabolic profiles of L6, C2C12, or primary human myotubes. Based on these distinct signatures, we provide recommendations for the appropriate use of these models depending on scientific hypotheses and biological relevance.