Resveratrol Enhances Self‐Renewal of Mouse Embryonic Stem Cells

Abstract

Resveratrol (RSV) has been shown to affect the differentiation of several types of stem cells, while the detailed mechanism is elusive. Here, we aim to investigate the function of RSV in self-renewal of mouse embryonic stem cells (ESCs) and the related mechanisms. In contrast with its reported roles, we found unexpectedly that differentiated ESCs or iPSCs treated by RSV would not show further differentiation, but regained a naïve pluripotency state with higher expressions of core transcriptional factors and with the ability to differentiate into all three germ layers when transplanted in vivo. In accordance with these findings, RSV also enhanced cell cycle progression of ESCs via regulating cell cycle-related proteins. Finally, enhanced activation of JAK/STAT3 signaling pathway and suppressed activation of mTOR were found essential in enhancing the self-renewal of ESCs by RSV. Our finding discovered a novel function of RSV in enhancing the self-renewal of ESCs, and suggested that the timing of treatment and concentration of RSV determined the final effect of it. Our work may contribute to understanding of RSV in the self-renewal maintenance of pluripotent stem cells, and may also provide help to the generation and maintenance of iPSCs in vitro. J. Cell. Biochem. 118: 1928-1935, 2017. © 2017 Wiley Periodicals, Inc.

Resveratrol enhances pluripotency of mouse embryonic stem cells by activating AMPK/Ulk1 pathway

“…There is little data uncovering resveratrol-dependent signaling pathways that regulate mESC pluripotency 16,33 . Here we show the mechanism of resveratrol action on pluripotency based on the mTORC1 pathway inhibition and autophagy activation via AMPK/Ulk1 (Figs.…”

Health benefits of resveratrol administration

“…Resveratrol induces neuronal differentiation in murine neuroblastoma cells (Namsi et al, 2018) and differentiation of monocytes to macrophages (Vasamsetti et al, 2016). Recent reports show that resveratrol increases self-renewal and maintains the pluripotency of human and mouse embryonic stem cells (Li et al, 2017;Safaeinejad et al, 2017). Intragastric administration or resveratrol causes activation of cardiac stem cells, an increase of capillary density, and reduction of apoptosis of cardiomyocytes, which may be beneficial in myocardial regeneration after acute myocardial infarction (Ling et al, 2017).…”

Resveratrol alleviates chemotherapy-induced oogonial stem cell apoptosis and ovarian aging in mice

“…From the perspective of telomeres, Res could attenuate telomere dysfunction through by activating Werner syndrome ATP-dependent helicase (WRN helicase), which contributes to telomere maintenance [48]. Furthermore, it has been reported that Res provides protective effects to damaged stem cells, such as embryonic stem cells (ESCs) [49], embryonic neural stem cells [50], and SSCs [17], by maintaining genomic stability and accelerating recovery from DSBs (double-strand breaks) [16]. However, there has been little research about whether Res has protective functions in a chemotherapy-induced ovarian aging model and whether Res could exert protective effects on female germline stem cells from apoptosis.…”