Li Zihong, Li Wei, Zhang Chenchen, Wang Jing, Geng Xiaoxiong, Qu Burong, Yue Yongli, Li Xueling
State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.
State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.
Int J Biol Macromol. 2025 Mar;295:139449. doi: 10.1016/j.ijbiomac.2024.139449. Epub 2025 Jan 3.
Human embryonic stem cells (hESCs) possess the ability to differentiate into various cell types, which is intricately linked to fatty acid synthesis and metabolism. Fatty acid desaturase 2 (FADS2) plays important role in fatty acid metabolism. In this study, we elucidate that the inhibition of FADS2 by SC-26196 enhances hESC pluripotency by upregulating key pluripotency genes such as POU5F1, NANOG, and KLF5. Moreover, SC-26196 treatment alters the fatty acid metabolic profile of hESCs, decreasing the synthesis of saturated fatty acids (SFAs) while increasing the content of monounsaturated fatty acids (MUFAs). Meanwhile, transcriptomic and proteomic analyses revealed that under FADS2 inhibition, hESCs maintain pluripotency primarily through enhanced oxidative phosphorylation and modified fatty acid metabolism. Knockdown and overexpression experiments confirm that FADS2 is a crucial regulator of these metabolic processes, and is essential for sustaining hESCs pluripotency. Collectively, this study unveils the pivotal role of FADS2 in the metabolic regulation of hESCs and provide new insights into the mechanisms governing pluripotency.
人类胚胎干细胞（hESCs）具有分化为各种细胞类型的能力，这与脂肪酸合成和代谢密切相关。脂肪酸去饱和酶2（FADS2）在脂肪酸代谢中起重要作用。在本研究中，我们阐明SC-26196对FADS2的抑制作用通过上调关键多能性基因如POU5F1、NANOG和KLF5来增强hESC的多能性。此外，SC-26196处理改变了hESCs的脂肪酸代谢谱，减少了饱和脂肪酸（SFAs）的合成，同时增加了单不饱和脂肪酸（MUFAs）的含量。同时，转录组学和蛋白质组学分析表明，在FADS2抑制下，hESCs主要通过增强氧化磷酸化和改变脂肪酸代谢来维持多能性。敲低和过表达实验证实FADS2是这些代谢过程的关键调节因子，对维持hESCs的多能性至关重要。总的来说，本研究揭示了FADS2在hESCs代谢调节中的关键作用，并为多能性调控机制提供了新的见解。
