Our knowledge of the molecular mechanisms surrounding human embryo implantation and gastrulation is lacking, largely due to technical and ethical limitations of experimenting with human embryos. Alternatives to human embryos have been reported, in which 3D clusters of embryonic stem cells are differentiated in a stepwise manner to model aspects of human embryogenesis. Yet it remains challenging to model the events past attachment. We propose a strategy of modeling the post-attachment human embryo by assembling a pre-formed polarized epithelial epiblast and extraembryonic cells, allowing them to self-organize into a structure that mimics the dish-attached human embryo. The model attaches in vitro and, in the absence of exogenous morphogens, breaks anteroposterior symmetry, giving rise to early gastrulation cell types. Our assembloid approach enables in a modular way to upgrade or exchange extraembryonic tissues to access more advanced stages of post-attachment development while complying with ethical policies.

我们缺乏关于人类胚胎植入和原肠胚形成的分子机制的知识，这主要是由于人类胚胎实验的技术和伦理限制。已经报道了人类胚胎的替代品，其中胚胎干细胞的 3D 簇以逐步方式分化以模拟人类胚胎发生的各个方面。然而，对过去的事件进行建模仍然具有挑战性。我们提出了一种通过组装预先形成的极化上皮外胚层和胚胎外细胞来模拟附着后人类胚胎的策略，使它们能够自我组织成一个模仿培养皿附着人类胚胎的结构。该模型在体外附着并且，在没有外源性形态发生素的情况下，会破坏前后对称性，从而产生早期原肠胚形成细胞类型。我们的组装方法能够以模块化的方式升级或交换胚胎外组织，以进入更高级的附着后发育阶段，同时遵守道德政策。