Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination

Abstract

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 and here we describe microRNA, miR-27a, expressed by OLs, as a regulator of OL development and survival. Increased levels of miR-27a was 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 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.