Mammalian post-implantation development comprises the coordination of complex lineage decisions and morphogenetic processes shaping the embryo. Despite technological advances, a comprehensive understanding of the dynamics of these processes and of the self-organization capabilities of stem cells and their descendants remains elusive. Building synthetic embryo-like structures from pluripotent embryonic stem cells in vitro promises to fill these knowledge gaps and thereby may prove transformative for developmental biology. Initial efforts to model the post-implantation embryo resulted in structures with compromised morphology (gastruloids). Recent approaches employing modified culture media, an extracellular matrix surrogate or extra-embryonic stem cells, however, succeeded in establishing embryo-like architecture. For example, embedding of gastruloids in Matrigel unlocked self-organization into trunk-like structures with bilateral somites and a neural tube-like structure, together with gut tissue and primordial germ cell-like cells. In this review, we describe the currently available models, discuss how these can be employed to acquire novel biological insights, and detail the imminent challenges for improving current models by in vitro engineering.

哺乳动物的植入后发育包括复杂的谱系决定和塑造胚胎的形态发生过程的协调。尽管技术进步，但对这些过程的动力学以及干细胞及其后代的自组织能力的全面了解仍然难以捉摸。从体外多能胚胎干细胞构建合成胚胎样结构有望填补这些知识空白，从而可能证明对发育生物学具有变革意义。对植入后胚胎进行建模​​的最初努力导致了形态受损的结构（类原肠胚）。然而，最近采用改良培养基、细胞外基质替代物或胚胎外干细胞的方法成功地建立了胚胎样结构。例如，在 Matrigel 中嵌入原肠胚可以解锁自组织成具有双侧体节和神经管样结构的躯干样结构，以及肠道组织和原始生殖细胞样细胞。在这篇综述中，我们描述了当前可用的模型，讨论如何利用这些模型来获得新的生物学见解，并详细说明通过体外改进当前模型的迫在眉睫的挑战。 工程。