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首页> 外文期刊>Molecular and Cellular Biology >The Transcription Factor TCFAP2C/AP-2γ Cooperates with CDX2 To Maintain Trophectoderm Formation
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The Transcription Factor TCFAP2C/AP-2γ Cooperates with CDX2 To Maintain Trophectoderm Formation

机译：转录因子TCFAP2C /AP-2γ与CDX2协同维持滋养层形成

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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.
机译：在哺乳动物中，细胞谱系规范是在胚泡期建立的。在此阶段，转录因子 Cdx2 抑制多能性基因，从而促进胚外滋养细胞的命运。最近，转录因子 Gata3 被证明在促进滋养层细胞命运中起着平行的作用，这表明在滋养层谱系中有更多的因子起作用。在这里，我们报道转录因子 Tcfap2c 在滋养外胚层中高水平表达，并能够诱导胚胎干细胞中的滋养层命运。由 Tcfap2c 诱导的滋养层命运不需要 Cdx2 ，反之亦然，这表明该分子以替代途径起作用。但是， Tcfap2c 和 Cdx2 都是滋养细胞干细胞维持标志物 Elf5 的上调所必需的，表明这两个因素对于稳定的滋养细胞诱导。 Tcfap2c 诱导的滋养细胞样细胞在长期培养中是稳定的，表明它们具有自我更新的能力。 Tcfap2c 控制的滋养细胞维持涉及 Cdx2 的诱导和多能性因子 Nanog的抑制。 Tcfap2c诱导的滋养细胞样细胞在体外分化为滋养细胞衍生物，并在体内囊胚中形成滋养外胚层。综上所述，这些观察结果表明， Tcfap2c 和 Cdx2 相互配合以覆盖多能性程序，并在鼠胚胎中建立了胚外滋养层维持程序。

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