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Role of Gltp in Maturation of Oligodendrocytes Under the Regulation of Nkx2.2

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Abstract

Myelin, a lipid-enriched multi-layer membrane structure, allows for rapid long-distance saltatory conduction of neuronal impulses. Although glycolipids are the predominant types of lipids in the myelin bilayer, the role of glycolipid transfer protein (GLTP), which selectively mediates the transfer of various glycolipids between phospholipid bilayer, in myelin development and maintenance remains unknown at present. In this study, we identified Gltp as the key lipid metabolism gene in myelin-forming oligodendrocytes (OLs) through integrated omics analysis across independent transcriptomic and single-cell sequencing studies. Gene expression analysis revealed that Gltp is selectively expressed in the differentiated OLs. Functional study demonstrated that its expression is essential for the differentiation of OLs, and promotes the outgrowth of OL membrane. Moreover, we found that the expression of Gltp is regulated by OL-lineage transcriptional factors, such as NKX2.2, OLIG2, SOX10, and MYRF. These findings provide important insights into the unrecognized functions of Gltp in OL differentiation and maturation.

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Data Availability

The datasets supporting the conclusions of this article are included within the article and its supplementary files.

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Funding

This work was supported by the Natural Science Foundation of Zhejiang Province (grants LQ23C090003) and the National Natural Science Foundation of China (grants 32170969).

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Authors and Affiliations

  1. Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second ** Wang

  2. Center for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China

    Chengfu Zhang

  3. Division of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China

    Zhen Chen

  4. Institute of Mental Health, Peking University Sixth Hospital, Bei**g, China

    Dai Zhang

  5. Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environment Sciences, Hangzhou Normal University, Hangzhou, China

    Mengsheng Qiu & Zhou Tan

Authors
  1. Chengfu Zhang
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  2. Zhen Chen
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  3. Dai Zhang
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  4. ** Wang
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  5. Mengsheng Qiu
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  6. Zhou Tan
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Contributions

Z.CF, CZ, and TZ performed the experiments; Z. CF and TZ designed the study; Z. CF and TZ wrote the manuscript; Q. MS, W. XP, and ZD revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhou Tan.

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All institutional and national guidelines for the care and use of laboratory animals were followed during the experiments. All procedures performed in this study observed the ethical standards of the Second **angya Hospital of Central South University and Hangzhou Normal University.

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Zhang, C., Chen, Z., Zhang, D. et al. Role of Gltp in Maturation of Oligodendrocytes Under the Regulation of Nkx2.2. Mol Neurobiol 60, 4897–4908 (2023). https://doi.org/10.1007/s12035-023-03383-y

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  • DOI: https://doi.org/10.1007/s12035-023-03383-y

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