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改变新陈代谢程序通过NAD+-依赖 deacetylation通过细胞的身份.
Robert A Bone1, Molly P Lowndes1,2, Silvia Raineri1
1Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
The EMBO journal
|April 25, 2025
概括
通过用银河糖取代葡萄糖来改变胚胎干细胞 (ESC) 的新陈代谢,促进了发育认同. 这种转变增强了氧化酸化 (OXPHOS),重新编程细胞以改善功能.
科学领域:
- 细胞生物学 细胞生物学
- 代谢重编程 代谢重编程
- 发展生物学 发展生物学
背景情况:
- 细胞代谢与基因调节密切相关.
- 了解代谢变化如何影响细胞身份对于发育生物学至关重要.
- 胚胎干细胞 (ESC) 具有独特的代谢特征,支持多能性.
研究的目的:
- 研究代谢变化如何在ESC中指导细胞身份.
- 探索氧化化 (OXPHOS) 在将ESC重编程到类似于内部细胞质 (ICM) 的状态中的作用.
- 阐明将代谢变化与转录编程联系起来的分子机制.
主要方法:
- 在介质中培养ESC,使用D-银糖而不是D-葡萄糖.
- 测量细胞代谢的变化,重点关注糖解和OXPHOS.
- 分析基因素和转录因子乙化水平.
- 评估基因表达和增强剂活性的变化.
主要成果:
- 用D-银糖替换D-葡萄糖可以抑制糖解并刺激ESC中的OXPHOS.
- 增强的OXPHOS激活了依赖NAD+的Sirtuin脱乙酶.
- 组织蛋白和转录因子的脱乙化聚焦了增强剂活性和减少了转录噪声.
- 这种代谢转变促进了类似于ICM的发育身份.
结论:
- 代谢重编程,特别是增强OXPHOS,可以诱导ESC中的特定发育细胞身份.
- 由OXPHOS调节的NAD+/NADH辅酶比率在编程谱系特异性转录中起着关键作用.
- 这种机制表明了通过有针对性的代谢和酶活性进行细胞复苏的范式.
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