Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, D-48149 Münster, Germany.
Cell Stem Cell. 2010 Mar 5;6(3):215-26. doi: 10.1016/j.stem.2010.01.003.
Mouse epiblast stem cells (EpiSCs) are cultured with FGF2 and Activin A, like human embryonic stem cells (hESCs), but the action of the associated pathways in EpiSCs has not been well characterized. Here, we show that activation of the Activin pathway promotes self-renewal of EpiSCs via direct activation of Nanog, whereas inhibition of this pathway induces neuroectodermal differentiation, like in hESCs. In contrast, the different roles of FGF signaling appear to be only partially conserved in the mouse. Our data suggest that FGF2 fails to cooperate with SMAD2/3 signaling in actively promoting EpiSC self-renewal through Nanog, in contrast to its role in hESCs. Rather, FGF appears to stabilize the epiblast state by dual inhibition of differentiation to neuroectoderm and of media-induced reversion to a mouse embryonic stem cell-like state. Our data extend the current model of cell fate decisions concerning EpiSCs by clarifying the distinct roles played by FGF signaling.
小鼠胚胎外胚层干细胞（EpiSCs）的培养需要 FGF2 和 Activin A，类似于人类胚胎干细胞（hESCs），但 EpiSCs 中相关通路的作用尚未得到很好的描述。在这里，我们发现激活 Activin 通路通过直接激活 Nanog 促进 EpiSCs 的自我更新，而抑制该通路则诱导神经外胚层分化，类似于 hESCs。相比之下，FGF 信号通路的不同作用在小鼠中似乎仅部分保守。我们的数据表明，FGF2 未能像在 hESCs 中那样，通过 Nanog 与 SMAD2/3 信号协同积极促进 EpiSC 的自我更新。相反，FGF 通过双重抑制向神经外胚层的分化和介质诱导的回复到类似于小鼠胚胎干细胞的状态，来稳定胚胎外胚层状态。我们的数据通过阐明 FGF 信号通路所发挥的不同作用，扩展了关于 EpiSCs 细胞命运决定的现有模型。
