Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination

• Published in: Cell reports (Cambridge) Vol. 29; no. 4; pp. 904 - 919.e9
• Main Authors: Tripathi, Ajai, Volsko, Christina, Garcia, Jessie P., Agirre, Eneritz, Allan, Kevin C., Tesar, Paul J., Trapp, Bruce D., Castelo-Branco, Goncalo, Sim, Fraser J., Dutta, Ranjan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.10.2019; Elsevier
• Subjects: miRNA; multiple sclerosis; oligodendrocyte progenitor cells; remyelination; miRNA; oligodendrocyte progenitor cells; multiple sclerosis; remyelination
• ISSN: 2211-1247; 2211-1247
• 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. [Display omitted] •miR-27a is expressed by OL lineage cells•Increased expression of miR-27a stalls OPCs at precursor stage•Higher levels of miR-27a is detected during demyelination•Exogenous administration of miR-27a leads to impaired developmental myelination and remyelination failure Generation of mature oligodendrocytes (OLs) from its progenitors is a controlled process. In this study, Tripathi et al. describes the role of miR-27a, expressed by oligodendrocyte lineage cells, in affecting multiple stages of this process. While miR-27a is needed for generation of mature OLs, increased levels of miR-27a is detected during demyelination and leads to failed remyelination.