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

Cell Rep. 2019 Mar 26;26(13):3784-3797.e8. doi: 10.1016/j.celrep.2019.02.105.

Abstract

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.

Keywords: lipids; miRNAs; mitochondria; single myofiber; skeletal muscle metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Gene Regulatory Networks
  • Glycogen / metabolism
  • Glycolysis
  • Humans
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mitochondria, Muscle / metabolism
  • Mitochondria, Muscle / ultrastructure
  • Muscle Fibers, Skeletal / metabolism*
  • Oxidative Phosphorylation
  • Transcriptome*

Substances

  • MIRN142 microRNA, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Glycogen