Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination

Cell Rep. 2019 Oct 22;29(4):904-919.e9. doi: 10.1016/j.celrep.2019.09.020.


Remyelination requires the generation of new oligodendrocytes (OLs), which are derived from oligodendrocyte progenitor cells (OPCs). Maturation of OPCs into OLs is a multi-step process. Here, we describe a microRNA expressed by OLs, miR-27a, as a regulator of OL development and survival. Increased levels of miR-27a were found in OPCs associated with multiple sclerosis (MS) lesions and in animal models of demyelination. Increased levels of miR-27a led to inhibition of OPC proliferation by cell-cycle arrest, as well as impaired differentiation of human OPCs (hOPCs) and myelination by dysregulating the Wnt-β-catenin signaling pathway. In vivo administration of miR-27a led to suppression of myelinogenic signals, leading to loss of endogenous myelination and remyelination. Our findings provide evidence supporting a critical role for a steady-state level of OL-specific miR-27a in supporting multiple steps in the complex process of OPC maturation and remyelination.

Keywords: miRNA; multiple sclerosis; oligodendrocyte progenitor cells; remyelination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myelin Sheath / metabolism*
  • Neurogenesis
  • Wnt Signaling Pathway


  • MIRN27 microRNA, human
  • MicroRNAs