The Transcription Factor TCFAP2C/AP-2γ Cooperates with CDX2 To Maintain Trophectoderm Formation
The Transcription Factor TCFAP2C/AP-2γ Cooperates with CDX2 To Maintain Trophectoderm Formation
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DOI：
10.1128/mcb.01215-09
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发表时间：
2010-07-01
影响因子：
5.3
通讯作者：
Schorle, Hubert
中科院分区：
文献类型：
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作者：
Kuckenberg, Peter;Buhl, Sandra;Schorle, Hubert
在哺乳动物中，细胞谱系特化在胚泡阶段建立。在这个阶段，转录因子Cdx2抑制多能性基因，从而促进胚外滋养层细胞的命运。最近，转录因子Gata3被证明在促进滋养层细胞命运的平行途径中起作用，这表明在滋养层谱系中有更多的因子起作用。在这里，我们报告说，转录因子Tcfap2c在滋养外胚层中以高水平表达，并能够诱导胚胎干细胞滋养层的命运。Tcfap2c诱导的滋养层细胞命运不需要Cdx2，反之亦然，这表明这些分子在替代途径中起作用。然而，Tcfap2c和Cdx2都是必需的ELF 5，滋养层干细胞维持的标志物的上调，这表明这两个因素都需要稳定的滋养层诱导。tcfap2c诱导的滋养层样细胞在长期培养中是稳定的，表明它们能够自我更新。Tcfap2c控制的滋养层维持涉及Cdx2的诱导和多能性因子Nanog的抑制。tcfap2c诱导的滋养层样细胞在体外分化为滋养层衍生物，并在体内促进囊胚中的滋养外胚层。总之，这些观察结果表明，Tcfap2c和Cdx2合作，以推翻多能性程序，并建立在小鼠胚胎的胚外滋养层维持程序。
In mammals, cell lineage specification is established at the blastocyst stage. At this stage, transcription factor Cdx2 represses pluripotency genes, thus promoting extraembryonic trophoblast fate. Recently, transcription factor Gata3 was shown to act in a parallel pathway in promoting trophoblast cell fate, suggesting that there are more factors working in the trophoblast lineage. Here, we report that the transcription factor Tcfap2c is expressed at a high level in the trophectoderm and is able to induce trophoblast fate in embryonic stem cells. Trophoblast fate induced by Tcfap2c does not require Cdx2 and vice versa, suggesting that the molecules act in alternative pathways. However, both Tcfap2c and Cdx2 are required for the upregulation of Elf5, a marker of trophoblast stem cell maintenance, suggesting that both factors are required for stable trophoblast induction. Tcfap2c-induced trophoblast-like cells are stable in long-term culture, indicating that they are capable of self-renewal. Tcfap2c-controlled trophoblast maintenance involves the induction of Cdx2 and the repression of the pluripotency factor Nanog. Tcfap2c-induced trophoblast-like cells differentiate to trophoblast derivatives in vitro and contribute to the trophectoderm in blastocysts in vivo. Taken together, these observations suggest that Tcfap2c and Cdx2 cooperate to override the pluripotency program and establish the extraembryonic trophoblast maintenance program in murine embryos.