Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway
Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway
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DOI：
10.1007/s12264-019-00376-7
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发表时间：
2019-04
影响因子：
5.6
通讯作者：
Yuchen Pan;Zeping Jiang;Dingya Sun;Zhenghao Li;Yingyan Pu;Dan Wang;Aijun Huang;Cheng He;Li Cao
中科院分区：
文献类型：
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作者：
Yuchen Pan;Zeping Jiang;Dingya Sun;Zhenghao Li;Yingyan Pu;Dan Wang;Aijun Huang;Cheng He;Li Cao
少突胶质前体细胞（OPCs）的正确分化对于中枢神经系统的髓鞘形成和髓鞘再生过程至关重要。确定调节机制是治疗脱髓鞘疾病的基础。通过分析不同神经细胞的RNA测序数据，我们发现细胞周期蛋白依赖性激酶18（cyclin-dependent kinase 18，CDK 18）只在少突胶质细胞中表达，体内研究表明，在发育过程中，CDK 18的表达水平沿着髓鞘形成而逐渐增加，在溶血磷脂酰胆碱诱导的脱髓鞘模型中，体外过表达和干扰实验表明，CDK 18直接促进OPCs的分化，而不影响OPCs的增殖和凋亡。在机制上，CDK 18激活RAS/促分裂原活化蛋白激酶激酶1/细胞外信号调节激酶途径，从而促进OPC分化。本研究的结果表明，CDK 18是一个有前途的细胞类型特异性靶点，以治疗脱髓鞘疾病。
The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes.In vivostudies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes.In vitrooverexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.