Dept. of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195, Berlin, Germany.
Dept. of Developmental Genetics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195, Berlin, Germany; Institute for Medical Genetics, Charité - University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
Dev Biol. 2021 Jun;474:5-15. doi: 10.1016/j.ydbio.2020.12.015. Epub 2020 Dec 29.
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.
哺乳动物着床后发育包括协调复杂的谱系决定和形态发生过程，从而塑造胚胎。尽管技术取得了进步，但对于这些过程的动态以及干细胞及其后代的自组织能力，我们仍难以全面理解。从多能胚胎干细胞体外构建合成的胚胎样结构有望填补这些知识空白，从而可能对发育生物学产生变革性的影响。最初尝试模拟着床后胚胎的结构导致形态受损的结构（胚状体）。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，将胚状体嵌入 Matrigel 中，可以解锁自我组织，形成具有双侧体节和神经管样结构的类似躯干的结构，同时还有肠道组织和原始生殖细胞样细胞。在这篇综述中，我们描述了目前可用的模型，讨论了如何利用这些模型获得新的生物学见解，并详细介绍了通过体外工程改进现有模型所面临的紧迫挑战。
