Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway

【Author】

Yuchen Pan;Zeping Jiang;Dingya Sun;Zhenghao Li;Yingyan Pu;Dan Wang;Aijun Huang;Cheng He;Li Cao;Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University;Department of Internal Medicine, Jiangsu Provincial Corps Hospital,Chinese People's Armed Police Force;

【Institution】

Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University;Department of Internal Medicine, Jiangsu Provincial Corps Hospital,Chinese People's Armed Police Force;

【Abstract】

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 vivo studies 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 vitro overexpression 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 kinase1/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.

【Keywords】

OPC;;Oligodendrocyte;;Myelination;;CDK18;;ERK

References

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Total: 21 articles

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