Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells.
Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells.
复制标题
使用三种类型的小鼠囊胚干细胞产生的自组装胚胎样结构的植入启动
DOI：
10.1038/s41467-019-08378-9
复制
发表时间：
2019
影响因子：
16.6
通讯作者：
Wang
中科院分区：
文献类型：
--
作者：
Zhang Shaopeng;Chen Tianzhi;Chen Naixin;Gao Dengfeng;Shi Bingbo;Kong Shuangbo;West Rachel Claire;Yuan Ye;Zhi Minglei;Wei Qingqing;Xiang Jinzhu;Mu Haiyuan;Yue Liang;Lei Xiaohua;Wang Xuepeng;Zhong Liang;Liang Hui;Cao Suying;Belmonte Juan Carlos Izpisua;Wang
由胚泡来源的干细胞自组装的空间有序的胚胎样结构可以在体外产生以模拟胚胎发生。然而，这种结构的组装体系和发展潜力还有待进一步研究。在这里，我们设计了一个非粘附悬浮振荡系统，以产生自组装胚胎样结构（ETX-胚状体）使用小鼠胚胎，滋养层和胚胎外内胚层干细胞。当一起培养时，这三种细胞类型聚集并分类成谱系特异性隔室。这些隔室之间的信号传导导致分子和形态发生事件，这些事件密切模仿在野生型胚胎中观察到的事件。这些ETX-胚状体表现出管腔形成、中胚层和原始生殖细胞前体标志物的基因表达的不对称模式以及前内脏内胚层样组织的形成。在移植到假孕小鼠子宫后，ETX-胚状体有效地启动植入并触发蜕膜组织的形成。这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一个强大的模型系统。
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.