Zhang Ye, Qi Xiu-Ming, Yao Yang-Ming, Liu Zhao-Hui, Xia Chun-Lin
Department of Anatomy and Cytoneurobiology Unit, Medical College of Soochow University, Suzhou, China,
Acta Neurobiol Exp (Wars). 2014;74(1):33-43. doi: 10.55782/ane-2014-1970.
Oligodendrocyte Precursor Cells (OPCs) can revert to multipotential Neural Stem-Like Cells (NSLCs) which can self-renew and give rise to neurons, astrocytes and oligodendrocytes when exposed to certain extracellular signals. This is a significant progress to understand developmental neurobiology, in particularly the possibility of converting glia to stem cells for the treatment of neurological disorders. Similarly, recent findings revealed that brain-resident microglias (MGs) can be converted to multipotential state through de-differentiation. In this study, we investigated the role of SRY (sex-determining region)-box 2 (SOX2), a high-mobility group DNA binding domain transcription factor, in the reprogramming of OPCs and MGs and molecular pathways involved in these process. Immunocytochemical analyses demonstrated that expression of SOX2 was upregulated in the reprogrammed MGs and OPCs as well as other neural stem cell markers such as CD15 and nestin. Western blot and double immunostaining analyses further confirmed that activation of bone morphogenetic proteins (BMPs) signaling partnering with SOX2 might be one of the molecular pathways involved in lineage reprogramming of OPCs which is also true in the reversion of MGs. Taken together, these results indicated that lineage reprogramming of OPCs and MGs are both controlled by the same signaling pathway and glia can be reprogrammed in culture by inducing expression of neurogenic transcription factors to transgress their lineage restriction and can stably acquire a neuronal identity. Our results suggested innovative perspectives for cell therapy with glia cells.
少突胶质前体细胞（OPCs）可以逆转为多能神经干细胞样细胞（NSLCs），当暴露于某些细胞外信号时，这些细胞能够自我更新并分化为神经元、星形胶质细胞和少突胶质细胞。这是理解发育神经生物学的一项重大进展，特别是在将胶质细胞转化为干细胞以治疗神经疾病方面的可能性。同样，最近的研究发现，脑内常驻的小胶质细胞（MGs）可以通过去分化转化为多能状态。在本研究中，我们调查了SRY（性别决定区）-盒2（SOX2），一种高迁移率族DNA结合域转录因子，在OPCs和MGs重编程中的作用以及这些过程中涉及的分子途径。免疫细胞化学分析表明，在重编程的MGs和OPCs以及其他神经干细胞标志物如CD15和巢蛋白中，SOX-2的表达上调。蛋白质免疫印迹和双重免疫染色分析进一步证实，与SOX2协同作用的骨形态发生蛋白（BMPs）信号通路的激活可能是参与OPCs谱系重编程的分子途径之一，这在MGs的逆转中也是如此。综上所述，这些结果表明，OPCs和MGs的谱系重编程均受相同信号通路的控制，可以通过诱导神经源性转录因子的表达在培养中对胶质细胞进行重编程，从而突破其谱系限制，并能稳定地获得神经元特性。我们的结果为胶质细胞的细胞治疗提供了创新的视角。
