Suvorova Irina I, Knyazeva Aleksandra R, Petukhov Alexey V, Aksenov Nicolay D, Pospelov Valery A
1Institute of Cytology, Russian Academy of Sciences, St-Petersburg, Russian Federation.
2Saint-Petersburg State University, St-Petersburg, Russian Federation.
Cell Death Discov. 2019 Feb 4;5:61. doi: 10.1038/s41420-019-0137-y. eCollection 2019.
Resveratrol, a natural polyphenolic compound, shows many beneficial effects in various animal models. It increases efficiency of somatic cell reprograming into iPSCs and contributes to cell differentiation. Here, we studied the effect of resveratrol on proliferation and pluripotency of mouse embryonic stem cells (mESCs). Our results demonstrate that resveratrol induces autophagy in mESCs that is provided by the activation of the AMPK/Ulk1 pathway and the concomitant suppression of the activity of the mTORC1 signaling cascade. These events correlate with the enhanced expression of pluripotency markers Oct3/4, Sox2, Nanog, Klf4, SSEA-1 and alkaline phosphatase. Pluripotency is retained under resveratrol-caused retardation of cell proliferation. Given that the Ulk1 overexpression enhances pluripotency of mESCs, the available data evidence that mTOR/Ulk1/AMPK-autophagy network provides the resveratrol-mediated regulation of mESC pluripotency. The capability of resveratrol to support the mESC pluripotency provides a new approach for developing a defined medium for ESC culturing as well as for better understanding signaling events that govern self-renewal and pluripotency.
白藜芦醇是一种天然多酚化合物，在多种动物模型中显示出许多有益作用。它提高了体细胞重编程为诱导多能干细胞（iPSC）的效率，并有助于细胞分化。在此，我们研究了白藜芦醇对小鼠胚胎干细胞（mESC）增殖和多能性的影响。我们的结果表明，白藜芦醇在mESC中诱导自噬，这是由AMPK/Ulk1途径的激活以及mTORC1信号级联活性的同时抑制所提供的。这些事件与多能性标志物Oct3/4、Sox2、Nanog、Klf4、SSEA-1和碱性磷酸酶的表达增强相关。在白藜芦醇引起的细胞增殖延迟情况下，多能性得以保留。鉴于Ulk1的过表达增强了mESC的多能性，现有数据证明mTOR/Ulk1/AMPK-自噬网络提供了白藜芦醇介导的mESC多能性调节。白藜芦醇支持mESC多能性的能力为开发用于ESC培养的限定培养基以及更好地理解控制自我更新和多能性的信号事件提供了一种新方法。
