Sox2 is essential for formation of trophectoderm in the preimplantation embryo.
Sox2 is essential for formation of trophectoderm in the preimplantation embryo.
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Sox2 对于植入前胚胎中滋养外胚层的形成至关重要。
DOI：
10.1371/journal.pone.0013952
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发表时间：
2010-11-12
期刊：
影响因子：
3.7
通讯作者：
Kimber SJ
中科院分区：
文献类型：
--
作者：
Keramari M;Razavi J;Ingman KA;Patsch C;Edenhofer F;Ward CM;Kimber SJ
在植入前哺乳动物发育中，转录因子Sox 2（SRY相关HMG盒基因2）与Oct 4形成复合物，并在维持多能性内细胞团（ICM）的自我更新中起作用。以前的研究表明，Sox 2 −/−胚胎在植入后很快死亡。然而，母体Sox 2转录本可能掩盖了早期的表型。我们研究了Sox 2是否参与控制细胞命运的决定在早期阶段。我们使用RNAi解决了Sox 2早期作用的问题，该RNAi去除了在植入前期间存在的母体和胚胎Sox 2 mRNA。通过在2-细胞阶段耗尽母体和胚胎Sox 2 mRNA并在体外监测胚胎发育，我们表明，在没有Sox 2的情况下，胚胎在桑椹胚阶段停滞，并且未能形成滋养外胚层（TE）或空化。在2细胞期小鼠胚胎中通过三种不同的短干扰RNA（siRNA）构建体敲低Sox 2后，我们已经表明大多数胚胎（76%）在桑椹胚期或稍早时停滞，并且与对照组中的76.2-83%相比，仅18.7-21%形成囊胚。在Sox 2 siRNA处理的胚胎中，多能性相关标志物Oct 4和Nanog的表达保持不受影响，而TE相关标志物Tead 4、雅普、Cdx 2、Eomes、Fgfr 2以及Fgf 4在不存在Sox 2的情况下下调。Sox 2基因敲低胚胎的凋亡率也增加。使用细胞渗透性Sox 2蛋白的拯救实验导致囊胚形成从18.7%增加到62.6%，并且在拯救的Sox 2-siRNA囊胚中恢复Sox 2、Oct 4、Cdx 2和雅普蛋白水平。我们的结论是Sox 2在植入前小鼠胚胎的第一个基本功能是促进滋养外胚层谱系的建立。我们的研究结果提供了一个新的见解植入前胚胎内的第一个分化事件，即ICM和TE谱系的分离。
In preimplantation mammalian development the transcription factor Sox2 (SRY-related HMG-box gene 2) forms a complex with Oct4 and functions in maintenance of self-renewal of the pluripotent inner cell mass (ICM). Previously it was shown that Sox2−/− embryos die soon after implantation. However, maternal Sox2 transcripts may mask an earlier phenotype. We investigated whether Sox2 is involved in controlling cell fate decisions at an earlier stage. We addressed the question of an earlier role for Sox2 using RNAi, which removes both maternal and embryonic Sox2 mRNA present during the preimplantation period. By depleting both maternal and embryonic Sox2 mRNA at the 2-cell stage and monitoring embryo development in vitro we show that, in the absence of Sox2, embryos arrest at the morula stage and fail to form trophectoderm (TE) or cavitate. Following knock-down of Sox2 via three different short interfering RNA (siRNA) constructs in 2-cell stage mouse embryos, we have shown that the majority of embryos (76%) arrest at the morula stage or slightly earlier and only 18.7–21% form blastocysts compared to 76.2–83% in control groups. In Sox2 siRNA-treated embryos expression of pluripotency associated markers Oct4 and Nanog remained unaffected, whereas TE associated markers Tead4, Yap, Cdx2, Eomes, Fgfr2, as well as Fgf4, were downregulated in the absence of Sox2. Apoptosis was also increased in Sox2 knock-down embryos. Rescue experiments using cell-permeant Sox2 protein resulted in increased blastocyst formation from 18.7% to 62.6% and restoration of Sox2, Oct4, Cdx2 and Yap protein levels in the rescued Sox2-siRNA blastocysts. We conclude that the first essential function of Sox2 in the preimplantation mouse embryo is to facilitate establishment of the trophectoderm lineage. Our findings provide a novel insight into the first differentiation event within the preimplantation embryo, namely the segregation of the ICM and TE lineages.
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DOI：
10.1073/pnas.95.9.5082
发表时间：
1998-04-28
影响因子：
11.1
作者：
Arman, E;Haffner-Krausz, R;Lonai, P
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Lonai, P
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Robson, Paul
影响因子：
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