Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel.
Cell Stem Cell. 2022 Oct 6;29(10):1445-1458.e8. doi: 10.1016/j.stem.2022.08.013. Epub 2022 Sep 8.
Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure.
已经开发了几种体外模型来仅从胚胎干细胞 (ESC) 中重现小鼠胚胎发生。尽管这些模型模拟了早期发育的许多方面，但它们未能捕捉到胚胎和胚胎外组织之间的相互作用。为了克服这一困难，我们开发了一种基于小鼠 ESC 的体外模型，通过转录因子介导的诱导来重建多能性 ESC 谱系和植入后胚胎的两个胚胎外谱系。该统一模型重现了从胚胎第 5.5 天到 8.5 天的发育事件，包括原肠胚形成；前-后轴、大脑和跳动的心脏结构的形成；以及胚胎外组织的发育，包括卵黄囊和绒毛膜。将个体结构的单细胞 RNA 测序与时间匹配的自然胚胎进行比较，在谱系之间鉴定出了非常相似的转录程序，但也显示了模型何时以及在何处与自然程序产生分歧。我们的研究结果表明，ESC 具有非凡的自组织能力，可以生成类似于整个胚胎的结构。
