Resveratrol promotes human embryonic stem cells self-renewal by targeting SIRT1-ERK signaling pathway

Abstract Resveratrol (RSV), a natural polyphenol component, has diverse biological properties. It has been shown that RSV regulated the self-renewal and differentiation of several types of stem cells, but the precise role of this compound on regulation of human embryonic stem cells (hESCs) self- renewal remained to be elucidated. Here we have shown that RSV promoted hESCs proliferation through cell cycle modulation and up-regulation of anti-apoptotic markers, without affecting pluripotency. Furthermore, inhibition of SIRT1 by EX-527 resulted in suppression of RSV-induced enhancement of hESCs self-renewal. RSV exerted its beneficial effects by activation of MEK/ERK signaling pathway as verified by application of specific MEK inhibitor, PD0325901. In conclusion, RSV elevated self-renewal of hESCs at least partly via “SIRT1-MEK/ERK” axis. These findings provide a novel application of RSV for developing a defined medium for hESCs culture which could help to better understanding of the signaling events that govern self-renewal of hESCs.