Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization^1,2,3. To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral–caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.

类肠胚是胚胎干细胞的三维聚集体，在植入后显示哺乳动物发育的关键特征，包括胚层规格和轴向组织^1,2,3. 迄今为止，只有少数基因在原肠胚中的表达模式已经用显微镜进行了探索，而原肠胚中的全基因组表达模式在多大程度上模仿了胚胎中的基因表达模式尚不清楚。在这里，我们使用单细胞 RNA 测序和空间转录组学比较小鼠原肠胚和小鼠胚胎。我们确定了以前不知道存在于原肠胚中的各种胚胎细胞类型，并表明体细胞发生的关键调节因子在胚胎和原肠胚之间的表达相似。使用实时成像，我们表明体细胞发生时钟在原肠胚中是活跃的，并且具有类似于体内的动力学。因为原肠胚可以大量生长，我们进行了一个小筛选，揭示了 FGF 信号传导的减少如何在胚胎中诱导短尾表型。最后，我们证明，嵌入基质胶会诱导原肠胚产生具有正确头端 - 尾端模式的体节，随着时间的推移，这些体节按前后方向顺序出现。因此，这项研究显示了原肠胚作为模型系统以高通量方式在体外探索发育和体细胞发生的能力。