Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination
2019
Ajai Tripathi | Christina Volsko | Jessie P. Garcia | Eneritz Agirre | Kevin C. Allan | Paul J. Tesar | Bruce D. Trapp | Goncalo Castelo-Branco | Fraser J. Sim | Ranjan Dutta
Summary: 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. : 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. Keywords: multiple sclerosis, remyelination, miRNA, oligodendrocyte progenitor cells
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