A critical role for miR-184 in the fate determination of oligodendrocytes

Negin Afrang,Rezvan Tavakoli,Amir Alian,Mehrnoosh Fathi-Roudsari,Farzad Rajaei,Alireza Naderi Sohi,Nooshin Tasharrofi,Mina Soufizomorrod,Masoud Soleimani,Mahboubeh Kabiri,Fatemeh Kouhkan

doi:10.1186/s13287-019-1208-y

Abstract

BackgroundNew insights on cellular and molecular aspects of both oligodendrocyte (OL) differentiation and myelin synthesis pathways are potential avenues for developing a cell-based therapy for demyelinating disorders comprising multiple sclerosis. MicroRNAs (miRNA) have broad implications in all aspects of cell biology including OL differentiation. MiR-184 has been identified as one of the most highly enriched miRNAs in oligodendrocyte progenitor cells (OPCs). However, the exact molecular mechanism of miR-184 in OL differentiation is yet to be elucidated.Methods and resultsBased on immunochemistry assays, qRT-PCR, and western blotting findings, we hypothesized that overexpression of miR-184 in either neural progenitor cells (NPCs) or embryonic mouse cortex stimulated the differentiation of OL lineage efficiently through regulating crucial developmental genes. Luciferase assays demonstrated that miR-184 directly represses positive regulators of neural and astrocyte differentiation, i.e., SOX1 and BCL2L1, respectively, including the negative regulator of myelination, LINGO1. Moreover, blocking the function of miR-184 reduced the number of committed cells to an OL lineage.ConclusionsOur data highlighted that miR-184 could promote OL differentiation even in the absence of exogenous growth factors and propose a novel strategy to improve the efficacy of OL differentiation, with potential applications in cell therapy for neurodegenerative diseases.

Highlights

New insights on cellular and molecular aspects of both oligodendrocyte (OL) differentiation and myelin synthesis pathways are potential avenues for developing a cell-based therapy for demyelinating disorders comprising multiple sclerosis
Our data highlighted that miR-184 could promote OL differentiation even in the absence of exogenous growth factors and propose a novel strategy to improve the efficacy of OL differentiation, with potential applications in cell therapy for neurodegenerative diseases
We report here for the first time that miR-184 can induce OL differentiation through directly targeting a number of genes such as sex-determining region Y (SRY)-Box 1 (SOX1), B cell lymphoma 2 (BCL2) Like 1 (BCL2L1), and leucine-rich repeat and immunoglobulin domain-containing Nogo receptor-interacting protein-1 (LINGO1), which have been previously shown to be highly expressed in neurons and astrocytes and involved in inhibiting oligodendrocyte precursor cells (OPCs) differentiation

Summary

Introduction

New insights on cellular and molecular aspects of both oligodendrocyte (OL) differentiation and myelin synthesis pathways are potential avenues for developing a cell-based therapy for demyelinating disorders comprising multiple sclerosis. There is no certain cure for this disease, and the majority of approved therapy such as glatiramer acetate, interferon-beta (IFN-β), and mitoxantrone mainly target the immunological aspects of MS [13] It is of high interest among researchers to develop a cure for MS that fights the disease by repairing the tissues and retrieving the disease. A smart approach, referred to as cell therapy, has been recently introduced that uses stem cells from the patient and differentiates them to oligodendrocyte precursor cells (OPCs) in order to regenerate the damaged tissues. This method has been employed by Thiruvalluvan et al, among others, and promising results have been achieved [14,15,16].

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