Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst.
Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst.
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DOI：
10.1016/j.devcel.2013.05.004
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发表时间：
2013-06-24
影响因子：
11.8
通讯作者：
Ralston, Amy
中科院分区：
文献类型：
--
作者：
Frum, Tristan;Halbisen, Michael A.;Wang, Chaoyang;Amiri, Hossein;Robson, Paul;Ralston, Amy
在胚胎干细胞和早期小鼠胚胎中，转录因子Oct4是多能性的重要调节因子。已经在胚胎干细胞系中描述了Oct4转录靶点；然而，Oct4调控外胚层（EPI）多能性建立的分子机制尚未完全阐明。在这里，我们发现无论是母系的还是合子的Oct4都不需要在囊胚中形成EPI细胞。相反，Oct4首先是原始内胚层（PE）发育所必需的，这是一种胚外谱系。EPI细胞通过分泌Fgf4促进邻近细胞的PE命运，而Oct4是Fgf4表达所必需的，但我们发现Oct4在Fgf4和Mapk的下游自主促进PE发育。最后，我们发现Oct4是多种EPI和PE基因的表达所必需的，也是着床前胚胎持续生长所必需的多种代谢途径的表达所必需的。
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 are required for 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 expression of multiple EPI and PE genes, as well as multiple metabolic pathways essential for the continued growth of the preimplantation embryo.
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