<scp>LPCAT1</scp>, the Enzyme Responsible for Converting <scp>LPC</scp> to <scp>PC</scp>, Promotes <scp>OPC</scp> Differentiation In Vitro

Myelin is the key structure for high-speed information transmission and is formed by oligodendrocytes (OLs) which are differentiated from oligodendrocyte precursor cells (OPCs) in the central nervous system. Lipid is the main component of myelin and the role of lipid metabolism-related molecules in myelination attach increasing attention. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) mediates the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), and its role in myelination draws our interest as LPC is a classical demyelination inducer and PC is a major component of myelin. In this work, LPCAT1 is found expressed in the oligodendrocyte lineage cells during myelination. In vitro experiments showed that the expression level of LPCAT1 gradually increased along with the differentiation process from OPCs to OLs, and over-expression and interference experiments showed that LPCAT1 promoted OPCs differentiation without affecting their proliferation or apoptosis. Mechanistically, the undertaker of LPCAT1's pro-differentiation role is not PC, but the phosphorylated mTOR which is a key regulator in OPCs differentiation. RNA sequencing analysis showed LPCAT1 promoted the expression of ZBTB20 which is an important transcription factor related to lipid metabolism and regulates mTOR phosphorylation. In vivo, complex myelin tomacula involving multiple axons was formed after conditionally knocking out LPCAT1 in oligodendrocyte lineage cells, but no obvious myelin thickness abnormalities were observed. Our results indicate that LPCAT1 is an important regulator of myelination, and lipid metabolism-related molecules may be new valuable targets for the treatment of diseases with myelin abnormalities.