Nakashima Kinichi, Kohyama Jun, Namihira Masakazu, Gage Fred H, Okano Hideyuki, Sawamoto Kazunobu
Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara.
No To Hattatsu. 2009 Nov;41(6):411-4.
Neural stem/progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes, and oligodendrocytes. It has become apparent that intracellular epigenetic modification including DNA methylation, in concert with extracellular cues such as cytokine signaling, is deeply involved in specifiying the fate of NSCs/NPCs by defining cell-type specific gene expression. However, it is still unclear how differentiated neural cells retain their specific attributes by repressing cellular properties characteristic of other lineages. In previous work, we have shown that methyl-CpG binding protein transcriptional repressors (MBDs), which were expressed predominantly in neurons in the central nervous system, inhibited astrocyte-specific gene expression by binding to highly methylated regions of their target genes. Here we report that oligodendrocytes, which do not express MBDs, can transdifferentiate into astrocytes both in vitro (cytokine stimulation) and in vive (ischemic injury) through the activation of the JAK/STAT signaling pathway. These findings suggest that differentiation plasticity in neural cells is regulated by cell-intrinsic epigenetic mechanisms in collaboration with ambient cell-extrinsic cues.
神经干细胞/祖细胞（NSCs/NPCs）可分化产生神经元、星形胶质细胞和少突胶质细胞。目前已明确，包括DNA甲基化在内的细胞内表观遗传修饰，与细胞因子信号传导等细胞外信号协同作用，通过定义细胞类型特异性基因表达，深度参与NSCs/NPCs的命运决定。然而，尚不清楚分化的神经细胞如何通过抑制其他谱系特征性的细胞特性来维持其特定属性。在之前的研究中，我们发现甲基化CpG结合蛋白转录抑制因子（MBDs）主要在中枢神经系统的神经元中表达，通过与靶基因的高度甲基化区域结合来抑制星形胶质细胞特异性基因表达。在此我们报告，不表达MBDs的少突胶质细胞可通过JAK/STAT信号通路的激活，在体外（细胞因子刺激）和体内（缺血性损伤）转分化为星形胶质细胞。这些发现表明，神经细胞的分化可塑性是由细胞内在表观遗传机制与周围细胞外信号协同调节的。
