Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells.,Nature Communications

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Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells.
Nature Communications ( IF 14.7 ) Pub Date : 2019-01-30 , DOI: 10.1038/s41467-019-08378-9
Shaopeng Zhang ₁ , Tianzhi Chen ₁ , Naixin Chen ₁ , Dengfeng Gao ₁ , Bingbo Shi ₁ , Shuangbo Kong ₂ , Rachel Claire West ₃ , Ye Yuan ₃ , Minglei Zhi ₁ , Qingqing Wei ₁ , Jinzhu Xiang ₁ , Haiyuan Mu ₁ , Liang Yue ₁ , Xiaohua Lei ₄ , Xuepeng Wang ₄ , Liang Zhong ₅ , Hui Liang ₁ , Suying Cao ₆ , Juan Carlos Izpisua Belmonte ₇ , Haibin Wang ₂ , Jianyong Han _{1,

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Affiliation

Spatially ordered embryo-like structures self-assembled from blastocyst-derived stem cells can be generated to mimic embryogenesis in vitro. However, the assembly system and developmental potential of such structures needs to be further studied. Here, we devise a nonadherent-suspension-shaking system to generate self-assembled embryo-like structures (ETX-embryoids) using mouse embryonic, trophoblast and extra-embryonic endoderm stem cells. When cultured together, the three cell types aggregate and sort into lineage-specific compartments. Signaling among these compartments results in molecular and morphogenic events that closely mimic those observed in wild-type embryos. These ETX-embryoids exhibit lumenogenesis, asymmetric patterns of gene expression for markers of mesoderm and primordial germ cell precursors, and formation of anterior visceral endoderm-like tissues. After transplantation into the pseudopregnant mouse uterus, ETX-embryoids efficiently initiate implantation and trigger the formation of decidual tissues. The ability of the three cell types to self-assemble into an embryo-like structure in vitro provides a powerful model system for studying embryogenesis.

中文翻译：

使用三种类型的小鼠胚泡来源的干细胞产生的自组装胚胎样结构的植入开始。

由胚泡衍生的干细胞自组装而来的空间有序的胚胎样结构可以在体外模拟胚胎发生。但是，这种结构的组装系统和发展潜力有待进一步研究。在这里，我们设计了一种非黏附悬浮液摇动系统，以使用小鼠胚胎，滋养细胞和胚外内胚层干细胞生成自组装的胚状结构（ETX胚状结构）。一起培养时，这三种细胞类型会聚集并分成特定于谱系的区室。这些区室之间的信号转导导致分子和形态发生事件，这些事件与野生型胚胎中观察到的事件非常相似。这些ETX胚状体表现出光亮，中胚层和原始生殖细胞前体标志物的基因表达不对称模式，内脏内胚层样组织的形成。移植到假孕小鼠子宫后，ETX-类胚激素有效地启动了植入并触发了蜕膜组织的形成。三种细胞类型在体外自组装成胚胎样结构的能力为研究胚胎发生提供了强大的模型系统。

更新日期：2019-01-30

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