Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Dev Cell. 2013 Jun 24;25(6):610-22. doi: 10.1016/j.devcel.2013.05.004. Epub 2013 Jun 6.
In embryonic stem (ES) cells and in early mouse embryos, the transcription factor Oct4 is an essential regulator of pluripotency. Oct4 transcriptional targets have been described in ES cell lines; however, the molecular mechanisms by which Oct4 regulates establishment of pluripotency in the epiblast (EPI) have not been fully elucidated. Here, we show that neither maternal nor zygotic Oct4 is required for the formation of EPI cells in the blastocyst. Rather, Oct4 is first required for development of the primitive endoderm (PE), an extraembryonic lineage. EPI cells promote PE fate in neighboring cells by secreting Fgf4, and Oct4 is required for expression of Fgf4, but we show that Oct4 promotes PE development cell-autonomously, downstream of Fgf4 and Mapk. Finally, we show that Oct4 is required for the expression of multiple EPI and PE genes as well as multiple metabolic pathways essential for the continued growth of the preimplantation embryo.
在胚胎干细胞和早期小鼠胚胎中，转录因子 Oct4 是多能性的必需调节因子。已经在胚胎干细胞系中描述了 Oct4 的转录靶标；然而，Oct4 调节外胚层（EPI）中多能性建立的分子机制尚未完全阐明。在这里，我们表明母源和合子 Oct4 都不是囊胚中 EPI 细胞形成所必需的。相反，Oct4 首先需要发育原始内胚层 (PE)，这是一种胚外谱系。EPI 细胞通过分泌 Fgf4 来促进邻近细胞的 PE 命运，而 Oct4 是 Fgf4 表达所必需的，但我们表明 Oct4 促进了 Fgf4 和 Mapk 下游的 PE 发育的自主性。最后，我们表明 Oct4 是多个 EPI 和 PE 基因以及多个代谢途径的表达所必需的，这些基因和代谢途径对于植入前胚胎的持续生长至关重要。
