Transcriptomic Analysis of Single Isolated Myofibers Identifies miR-27a-3p and miR-142-3p as Regulators of Metabolism in Skeletal Muscle

Transcriptomic Analysis of Single Isolated Myofibers Identifies miR-27a-3p and miR-142-3p as Regulators of Metabolism in Skeletal Muscle
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DOI:
10.1016/j.celrep.2019.02.105
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发表时间:
2019-03-26
期刊:
影响因子:
8.8
通讯作者:
Lanfranchi, Gerolamo
Lanfranchi, Gerolamo
中科院分区:
生物学1区
文献类型:
--
作者:
Chemello, Francesco;Grespi, Francesca;Lanfranchi, Gerolamo

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骨骼肌由不同类型的肌纤维组成,这些肌纤维优先使用葡萄糖或脂质来产生ATP。这些有丝分裂后细胞的燃料偏好是如何调节的,这在很大程度上是未知的,这使得这个问题成为肌肉和全身代谢领域的一个关键问题。在这里,我们展示了microRNAs (miRNAs)在定义肌纤维代谢谱中发挥作用。在单细胞水平上获得的所有肌纤维类型的mRNA和miRNA特征揭示了纤维特异性调节网络,并确定了协调控制肌纤维燃料偏好和线粒体形态的两个主要miRNA。我们的工作提供了一个完整和集成的小鼠肌纤维类型特异性基因和miRNA表达目录,并建立了miR-27a-3p和miR-142-3p作为骨骼肌脂质使用的调节因子。
Skeletal muscle is composed of different myofiber types that preferentially use glucose or lipids for ATP production. How fuel preference is regulated in these post-mitotic cells is largely unknown, making this issue a key question in the fields of muscle and whole-body metabolism. Here, we show that microRNAs (miRNAs) play a role in defining myofiber metabolic profiles. mRNA and miRNA signatures of all myofiber types obtained at the single-cell level unveiled fiber-specific regulatory networks and identified two master miRNAs that coordinately control myofiber fuel preference and mitochondrial morphology. Our work provides a complete and integrated mouse myofiber type-specific catalog of gene and miRNA expression and establishes miR-27a-3p and miR-142-3p as regulators of lipid use in skeletal muscle.