Early preimplantation cells expressing Cdx2 exhibit plasticity of specification to TE and ICM lineages through positional changes.

Early preimplantation cells expressing Cdx2 exhibit plasticity of specification to TE and ICM lineages through positional changes.
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表达 Cdx2 的早期植入前细胞通过位置变化表现出 TE 和 ICM 谱系的可塑性。

DOI:
10.1016/j.ydbio.2016.01.011
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发表时间:
2016
期刊:
Dev Biol.
影响因子:
--
通讯作者:
T.
T.
中科院分区:
--
文献类型:
--
作者:
Toyooka;Y.;Oka;S.;and Fujimori;T.

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滋养外胚层(TE)和内细胞团(ICM)的建立是小鼠着床前发育中第一次发生细胞谱系分离。这两种细胞系在胚泡阶段以一种位置依赖的方式出现:外层细胞形成TE,形成未来的胎盘;而内部细胞形成ICM,由此产生上胚层(EPI)和原始内胚层(PRE)。先前的研究表明,在植入前阶段,部分细胞从外向内迁移,但很少有研究探讨细胞迁移与细胞分化关键转录因子表达之间的相关性。为了监测活胚胎中细胞的运动和TE规范通路的状态,我们建立了CDX2-GFP报告小鼠,使我们能够可视化尾型转录因子(CDX2)的表达,CDX2是启动TE分化的关键调节因子。对植入前胚胎的活体细胞成像观察表明,所有定位于初始外部位置的细胞都启动了CDx2的表达,随后,从外部位置改变为内部位置的细胞下调了CDx2的表达,从而促进了ICM的形成。最后,我们发现内化细胞可能对EPI和Pre都有贡献。我们的数据表明,即使表达高水平的CDX2的细胞也可以内化、失活激活的TE规范的分子通路,并整合到多能细胞群中。
The establishment of the trophectoderm (TE) and the inner cell mass (ICM) is the first cell lineage segregation to occur in mouse preimplantation development. These two cell lineages arise in a position-dependent manner at the blastocyst stage: the outer cells form TE, which will generate the future placenta, while the inner cells give rise to the ICM, from which the epiblast (EPI) and primitive endoderm (PrE) arise. Previous studies have shown that a portion of cells relocate from the outside position to the inside during this preimplantation stage, but few studies have investigated the correlation between cell relocation and the expression of key transcription factors critical for cell differentiation. To monitor cell movement and the status of the TE-specification pathway in living embryos, we establishedCdx2-GFP reporter mice allowing us to visualize the expression of Caudal-type transcriptional factor (Cdx2), a key regulator of the initiation of TE differentiation. Observation of Cdx2-GFP preimplantation embryos by live cell imaging revealed that all cells localized in an initial outer position initiated the expression ofCdx2.Subsequently, cells that changed their position from an outer to an inner position downregulatedCdx2expression and contributed to the ICM. Finally we showed that internalized cells likely contribute to both the EPI and PrE. Our datas indicate that cells expressing even high levels ofCdx2can internalize, deactivate an activated TE-specification molecular pathway and integrate into the pluripotent cell population.
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