MicroRNA-Mediated In Vitro and In Vivo Direct Conversion of Astrocytes to Neuroblasts

Background The conversion of astrocytes to neuroblasts holds great promise for treatment of neurodegenerative and traumatic brain diseases. Methodology and Principal Findings Here we have shown that adult human astrocytes could be reprogrammed to neuroblasts by miR-302/367, both in vivo and in vitro. However, the reprogramming of adult mouse astrocytes to neuroblasts required valproic acid (VPA), a histone deacetylase inhibitor. Following induction of astrocytes toward neurons the expression of pluripotency markers were not detected, which suggested direct cell conversion. We did not observed tumor formation during two months follow up. Conclusions and Significance These results show that neuroblasts can be generated directly from adult human and mouse astrocytes by miR-302/367-driven induction. This approach seems promising for converting glial scar cells into neuroblasts in a wide range of neurological diseases.研究背景 星形胶质细胞（astrocytes）向成神经细胞（neuroblasts）的转化，在神经退行性疾病与创伤性脑疾病的治疗领域拥有极高的应用潜力。 研究方法与主要发现 本文证实，miR-302/367可在体内（in vivo）与体外（in vitro）环境中将成人星形胶质细胞重编程为成神经细胞。然而，将成年小鼠星形胶质细胞重编程为成神经细胞则需要丙戊酸（valproic acid, VPA）——一种组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitor）的参与。在诱导星形胶质细胞向神经元转化的过程中，未检测到多能性标志物（pluripotency markers）的表达，这表明该过程属于直接细胞转分化。在为期两个月的随访期间，未观察到肿瘤形成。 结论与意义 本研究结果表明，通过miR-302/367介导的诱导，可直接从成人及小鼠星形胶质细胞中获得成神经细胞。该方法在多种神经系统疾病中，有望将胶质瘢痕细胞（glial scar cells）转化为成神经细胞，具备良好的应用前景。