PRMT3介导的甲基化修饰在胚胎干细胞分化过程中的作用及机制研究
精氨酸甲基化是一种常见的蛋白质翻译后修饰方式,由蛋白精氨酸甲基转移酶(Protein arginine methyltransferases, PRMTs)家族蛋白催化完成。PRMTs通过甲基化其胞质或细胞核内的特异性底物,调控细胞分化、胚胎发育和糖脂代谢等多种生物学过程。近年来的研究表明,PRMT的表达异常与多种癌症发生发展密切相关,因此受到广泛关注。PRTM3作为一种独特的PRMT,其广泛表达于多种细胞类型,但PRMT3在胚胎干细胞(Embryonic Stem Cells, ESCs)中调控分化过程的生物学功能仍然未知。本研究以小鼠胚胎干细胞(mouse ESCs, mESCs)分化为拟胚体(Embryoid Body, EB)为研究模型,探究PRMT3在ESCs分化过程中的作用及具体分子机制。研究结果表明,在诱导ESCs分化为EB的过程中抑制PRMT3,将会特异性下调神经外胚层相关标志蛋白NESTIN、SOX2和PAX6的表达水平,同时降低糖脂代谢相关酶FASN、SCD1和PKM1/2的表达水平。相反,过表达PRMT3则可上调NESTIN、FASN和SCD1的表达水平。综上所述,本研究结果暗示PRMT3可能通过调控糖脂代谢,进而影响ESCs向神经外胚层的分化过程。
rginine methylation is a common post-translational modification of proteins, catalyzed by the Protein arginine methyltransferases (PRMTs) family of proteins. PRMTs regulate a variety of biological processes such as cell differentiation, embryonic development, and glycolipid metabolism, through methylation of their cytoplasmic or nucleus-specific substrates. biological processes. As a unique PRMT, PRTM3 is widely expressed in various cell types, but the biological function of PRMT3 in regulating differentiation processes in Embryonic Stem Cells (ESCs) remains unknown. In this study, we used the differentiation of mouse ESCs (mESCs) into Embryoid Body (EB) as a research model to investigate the role of PRMT3 in the differentiation process of ESCs and the specific molecular mechanism. The results showed that inhibition of PRMT3 during the induction of ESCs differentiation into EBs would specifically down-regulate the expression levels of the neural ectoderm-related marker proteins NESTIN, SOX2, and PAX6, as well as decrease the expression levels of the enzymes related to glycolipid metabolism FASN, SCD1, and PKM1/2. In contrast, overexpression of PRMT3 upregulated the expression levels of NESTIN, FASN, and SCD1. Taken together, the results of the present study imply that PRMT3 may affect the differentiation process of ESCs to neural ectoderm through the regulation of glycolipid metabolism, and then affect the differentiation process of ESCs to neural ectoderm.
钱佳婷、贾志浩
苏州大学苏州医学院剑桥-苏大基因组资源中心,江苏省苏州市 215123苏州大学苏州医学院剑桥-苏大基因组资源中心,江苏省苏州市 215123
细胞生物学
细胞生物学胚胎干细胞PRMT3NESTINFASN糖脂代谢
Cell biologyEmbryonic stem cellPRMT3NESTINFASNGlucolipid metabolism
钱佳婷,贾志浩.PRMT3介导的甲基化修饰在胚胎干细胞分化过程中的作用及机制研究[EB/OL].(2025-04-15)[2025-07-03].http://www.paper.edu.cn/releasepaper/content/202504-145.点此复制
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