PDF(Pubmed)
Abstract：
The transcription factor Sox10 is an important determinant of oligodendroglial identity and influences oligodendroglial development and characteristics at various stages. Starting from RNA-seq data, we here show that the expression of several voltage-gated ion channels with known expression and important function in oligodendroglial cells depends upon Sox10. These include the Nav1.1, Cav2.2, Kv1.1, and Kir4.1 channels. For each of the four encoding genes, we found at least one regulatory region that is activated by Sox10 in vitro and at the same time bound by Sox10 in vivo. Cell-specific deletion of Sox10 in oligodendroglial cells furthermore led to a strong downregulation of all four ion channels in a mouse model and thus in vivo. Our study provides a clear functional link between voltage-gated ion channels and the transcriptional regulatory network in oligodendroglial cells. Furthermore, our study argues that Sox10 exerts at least some of its functions in oligodendrocyte progenitor cells, in myelinating oligodendrocytes, or throughout lineage development via these ion channels. By doing so, we present one way in which oligodendroglial development and properties can be linked to neuronal activity to ensure crosstalk between cell types during the development and function of the central nervous system.
摘要：
转录因子Sox10是少突胶质细胞身份的重要决定因素，并在各个阶段影响少突胶质细胞的发育和特征。从RNA-seq数据开始，我们在这里表明，在少突胶质细胞中具有已知表达和重要功能的几种电压门控离子通道的表达取决于Sox10。其中包括Nav1.1、Cav2.2、Kv1.1和Kir4.1通道。对于四个编码基因中的每一个，我们发现至少一个调控区在体外被Sox10激活，同时在体内被Sox10结合。少突胶质细胞中Sox10的细胞特异性缺失还导致小鼠模型中所有四种离子通道的强烈下调，因此在体内。我们的研究提供了电压门控离子通道和少突胶质细胞转录调控网络之间的明确功能联系。此外，我们的研究认为，Sox10在少突胶质细胞祖细胞中至少发挥了一些功能，在髓鞘少突胶质细胞中，或通过这些离子通道在整个谱系发育过程中。通过这样做,我们提出了一种方法，其中少突神经胶质的发育和特性可以与神经元活动联系起来，以确保在中枢神经系统发育和功能过程中细胞类型之间的串扰。
