小柯机器人

英国剑桥大学Magdalena Zernicka-Goetz研究组发现，合成胚胎可完成从胚胎发育到神经和器官形成的过程。2022年8月25日，《自然》杂志在线发表了这项成果。

研究人员表示，胚胎干细胞（ESC）可以在体外经历哺乳动物胚胎发育的许多方面，但它们的发育潜力通过与胚胎外干细胞，包括滋养层干细胞（TSC）、胚胎外内胚层干细胞（XEN）和可诱导的XEN细胞（iXEN）的相互作用而大大延长。

研究人员用小鼠ESC、TSC和iXEN细胞在体外组装了干细胞衍生的胚胎，并显示它们再现了整个自然小鼠胚胎在子宫内的发育过程，直到第8.5天。这个胚胎模型显示出具有明确的前脑和中脑区域的头褶，并发育出一个类似心脏跳动的结构，一个由神经管和体细胞组成的躯干，一个含有神经外胚层祖细胞的尾芽，一个肠管，以及原始生殖细胞。这个完整的胚胎模型在启动血岛发育的胚胎外卵黄囊内发育。

重要的是，研究人员证明了由Pax6基因敲除ESC与野生型TSC和iXEN聚集而成的神经管胚胎模型再现了自然的、普遍的Pax6基因敲除胚胎中发生的神经管腹侧域扩张。因此，这些完整的胚胎是一个强大的体外模型，可用于剖析不同谱系和基因在发育中的作用。这些结果证明了胚胎和两种胚胎外干细胞的自我组织能力，可通过和超越原肠运动到神经元和早期器官形成来重建哺乳动物的发育。

附：英文原文

Title: Synthetic embryos complete gastrulation to neurulation and organogenesis

Author: Amadei, Gianluca, Handford, Charlotte E., Qiu, Chengxiang, De Jonghe, Joachim, Greenfeld, Hannah, Tran, Martin, Martin, Beth K., Chen, Dong-Yuan, Aguilera-Castrejon, Alejandro, Hanna, Jacob H., Elowitz, Michael, Hollfelder, Florian, Shendure, Jay, Glover, David M., Zernicka-Goetz, Magdalena

Issue&Volume: 2022-08-25

Abstract: Embryonic stem cells (ESC) can undergo many aspects of mammalian embryogenesis in vitro1–5, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem cells (TSCs), extraembryonic endoderm stem cells (XEN), and inducible-XEN cells (iXEN)6–11. Here, we assembled stem-cell derived embryos in vitro from mouse ESCs, TSCs and iXEN cells and showed that they recapitulate whole natural mouse embryo development in utero to day 8.5. Our embryo model displays head-folds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extra-embryonic yolk sac that initiates blood island development. Importantly, we demonstrate that the neurulating embryo model assembled from Pax6 knockout-ESCs aggregated with wild-type TSCs and iXENs recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6 knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse lineages and genes in development. Our results demonstrate the self-organization ability of embryonic and two types of extra-embryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.

DOI: 10.1038/s41586-022-05246-3

Source: https://www.nature.com/articles/s41586-022-05246-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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