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.
摘要:
Myelin,富含脂质的多层膜结构,允许神经元冲动的快速长距离盐分传导。尽管糖脂是髓磷脂双层中的主要脂质类型,糖脂转移蛋白(GLTP)的作用,选择性介导磷脂双层之间各种糖脂的转移,髓鞘的发育和维持目前尚不清楚。在这项研究中,通过独立转录组和单细胞测序研究的整合组学分析,我们将Gltp鉴定为髓鞘形成少突胶质细胞(OLs)的关键脂质代谢基因.基因表达分析揭示Gltp在分化的OL中选择性表达。功能研究表明,其表达对OLs的分化至关重要,并促进OL膜的生长。此外,我们发现Gltp的表达受OL谱系转录因子的调控,如NKX2.2、OLIG2、SOX10和MYRF。这些发现为Gltp在OL分化和成熟中的未识别功能提供了重要见解。