Laboratory of Synthetic Embryology, The Rockefeller University, New York, NY 10065, USA; Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10065, USA; Department of Chemical Engineering, Columbia University, New York, NY 10025, USA; Department of Genetics and Development, Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA.
Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10065, USA.
Cell Stem Cell. 2022 Jun 2;29(6):962-972.e4. doi: 10.1016/j.stem.2022.05.001.
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.
我们对人类胚胎着床和原肠胚形成相关分子机制的了解还很缺乏，这主要是由于用人类胚胎进行实验存在技术和伦理方面的限制。已经有报道称，可以使用替代人类胚胎的方法，即将胚胎干细胞 3D 簇逐步分化，以模拟人类胚胎发生的某些方面。然而，要模拟附着后的胚胎事件仍然具有挑战性。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，使它们能够自行组织成类似于附着在培养皿上的人类胚胎的结构。该模型在体外附着，并且在没有外源形态发生素的情况下，打破前-后对称，产生早期原肠胚细胞类型。我们的组装方法以模块化的方式升级或更换胚胎外组织，以进入附着后发育的更高级阶段，同时符合伦理政策。
