Sevoflurane represses the self‐renewal ability by regulating miR‐7a,7b/Klf4 signalling pathway in mouse embryonic stem cells

Sevoflurane is a frequently‐used clinical inhalational anaesthetic and can cause toxicity to embryos during foetal development. Embryonic stem cells (ESCs) are derived from the inner cell mass of blastospheres and can be used as a useful model of early development. Here, we found that sevoflurane significantly influenced self‐renewal ability of mESCs on stemness maintenance and cell proliferation. The cell cycle was arrested via G1 phase delay. We further found that sevoflurane upregulated expression of miR‐7a,7b to repress self‐renewal. Next we performed rescue experiments and found that after adding miR‐7a,7b inhibitor into mESCs treated with sevoflurane, its influence on self‐renewal could be blocked. Further we identified stemness factor Klf4 as the direct target of miR‐7a,7b. Overexpression of Klf4 restored self‐renewal ability repressed by miR‐7a,7b or sevoflurane. In this work, we determined that sevoflurane repressed self‐renewal ability by regulating the miR‐7a,7b/Klf4 signalling pathway in mESCs. Our study demonstrated molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on safe usage of inhalational anaesthetic during non‐obstetric surgery.     

Klf4的功能研究进展

Klf4作为真核生物转录因子,参与调控细胞增殖、分化、胚胎发育等重要生命过程,是体细胞重编程为诱导多能干细胞（iPS细胞）的重要诱导因子之一。本文综述了Klf4在细胞增殖、分化、肿瘤发生、皮肤屏障、热休克及iPS细胞诱导等方面的研究进展,为深入研究Klf4在重编程中的作用机制和功能提供参考。