Atmospheric pressure plasma irradiation on embryonic stem cells: Signals and differentiation

Abstract

Mouse embryonic stem cells (ESCs) are pluripotent stem cells (PSCs) derived from pre-implantation embryos. They possess self-renewal properties in vitro and can differentiate into various types of cells. Signaling via extrinsic factors is one of the main factors that determine cell fate during the differentiation of PSCs. For example, fibroblast growth factor (FGF) signal enhances the differentiation of ESCs into ectoderm and neural stem cells in mice and in humans. Recently, reactive oxygen species (ROS) have been reported to regulate various signaling pathways. A large number of reactive species such as ROS and reactive nitrogen species are generated by atmospheric pressure plasma (APP) irradiation. We analyzed the effects of APP irradiation on the maintenance and differentiation of mouse ESCs, focusing on signal control. We found that APP irradiation inhibited the proliferation of mouse ESCs, but did not affect their undifferentiated state. In contrast, APP irradiation did not inhibit the proliferation of embryoid bodies, but did inhibit the differentiation of mouse ESCs to mesoderm and endoderm by inhibiting Wnt signal. APP irradiation enhanced the differentiation to the epiblast, ectoderm, and neuronal lineages by activation of FGF4 signaling. This suggests that the latter effects are caused by the H2O2 generated in the medium by APP irradiation.