近日，英国剑桥大学Magdalena Zernicka-Goetz及其研究组开发出来自多能干细胞的植入后人类胚胎模型。2023年6月27日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员建立了一个由胚胎和胚胎外组织组成的人类植入后胚胎模型，即人类类胚胎。研究人员将转录因子过量表达产生的两种胚外样细胞与野生型胚胎干细胞结合起来，并促进它们自组织成模仿植入后人类胚胎的几方面结构。这些自组织的聚合体包含一个被胚胎外组织包围的多能的外胚层样域。功能研究表明，在BMP的提示下，外胚层样域会有力地分化为羊膜、胚外间质和原始生殖细胞样细胞。此外，研究人员确定了SOX17在前部下胚层类细胞特化中的抑制作用。下胚层样细胞区的亚群调控表明，胚外样细胞影响上胚层样细胞域的分化，突出了组织与组织之间的功能交流。

总之，研究人员提出了一个模块化的、可操作的、综合的人类胚胎模型，这将使人们能够探究人类植入后发育的关键问题，这是大量怀孕失败的一个关键窗口。

据介绍，人类胚胎在植入子宫后经历了形态发生的转变，但由于无法在体内观察胚胎，人们对这一关键阶段的认识是有限的。干细胞衍生的胚胎模型是揭示这些阶段的发育事件和组织-组织交流的重要工具。

附：英文原文

Title: A model of the post-implantation human embryo derived from pluripotent stem cells

Author: Weatherbee, Bailey A. T., Gantner, Carlos W., Iwamoto-Stohl, Lisa K., Daza, Riza M., Hamazaki, Nobuhiko, Shendure, Jay, Zernicka-Goetz, Magdalena

Issue&Volume: 2023-06-27

Abstract: The human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Stem cell-derived models of the embryo are important tools to interrogate developmental events and tissue-tissue crosstalk during these stages1. Here, we establish a model of the human post-implantation embryo, a human embryoid, comprised of embryonic and extraembryonic tissues. We combine two types of extraembryonic-like cells generated by transcription factor overexpression with wildtype embryonic stem cells and promote their self-organization into structures that mimic several aspects of the post-implantation human embryo. These self-organized aggregates contain a pluripotent epiblast-like domain surrounded by extraembryonic-like tissues. Our functional studies demonstrate that the epiblast-like domain robustly differentiates to amnion, extraembryonic mesenchyme, and primordial germ cell-like cells in response to BMP cues. In addition, we identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells2. Modulation of the subpopulations in the hypoblast-like compartment demonstrated that extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, we present a modular, tractable, integrated3 model of the human embryo that will allow us to probe key questions of human post-implantation development, a critical window when significant numbers of pregnancies fail.

DOI: 10.1038/s41586-023-06368-y

Source: https://www.nature.com/articles/s41586-023-06368-y