Stem Cell Technology Research Center, P.O. Box: 15856-36473, Tehran, Iran.
School of Paramedical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran.
Stem Cell Res Ther. 2019 Mar 29;10(1):112. doi: 10.1186/s13287-019-1208-y.
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. 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.
Based 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.
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.
在少突胶质细胞（OL）分化和髓鞘合成途径的细胞和分子方面的新见解，为开发针对多发性硬化症等脱髓鞘疾病的基于细胞的治疗方法提供了潜在途径。微小 RNA（miRNA）在细胞生物学的各个方面都有广泛的影响，包括 OL 分化。miR-184 已被确定为少突胶质前体细胞（OPC）中最丰富的 miRNA 之一。然而，miR-184 在 OL 分化中的确切分子机制尚待阐明。
基于免疫化学测定、qRT-PCR 和 Western blot 发现，我们假设在神经祖细胞（NPC）或胚胎鼠皮层中过表达 miR-184 可以通过调节关键发育基因有效地刺激 OL 谱系的分化。荧光素酶测定表明，miR-184 分别直接抑制神经和星形胶质细胞分化的正调控因子 SOX1 和 BCL2L1，包括髓鞘形成的负调控因子 LINGO1。此外，阻断 miR-184 的功能会减少向 OL 谱系分化的细胞数量。
我们的数据强调了 miR-184 可以促进 OL 分化，即使在没有外源性生长因子的情况下，也为提高 OL 分化的效率提供了一种新的策略，这可能为神经退行性疾病的细胞治疗提供了应用。
