Self-organization of the in vitro attached human embryo
Self-organization of the in vitro attached human embryo
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DOI：
10.1038/nature17948
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发表时间：
2016-05-12
期刊：
影响因子：
64.8
通讯作者：
Brivanlou, Ali H.
中科院分区：
文献类型：
--
作者：
Deglincerti, Alessia;Croft, Gist F.;Brivanlou, Ali H.
胚泡的植入是哺乳动物胚胎发育的一个里程碑。此时，谱系多样化、细胞命运特化和形态发生运动的协调程序建立了胚外组织和胚胎本身的产生，并决定了成功妊娠和原肠胚形成的条件。尽管它的基本和临床重要性，这一过程在人类中仍然是神秘的。在这里，我们报告了使用一种新的体外系统（1，2）来研究人类胚胎的植入后发育。我们揭示了体外附着的人类胚胎的自组织能力和自主性。我们发现了人类特异性的早期细胞谱系、时间和结构的分子特征。胚胎显示正常发育的关键标志，包括上胚层扩张、谱系分离、双层盘形成、羊膜和卵黄囊空化以及滋养层多样化。我们的研究结果突出了这些发育事件的物种特异性，并提供了一个新的理解早期人类胚胎发育超过囊胚阶段。此外，我们的研究建立了一个新的模型系统相关的早期人类妊娠丢失。最后，我们的工作也将有助于合理设计人类胚胎干细胞分化为特定细胞类型的方案，用于疾病建模和细胞替代治疗。
Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system(1,2) to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy.