Essential genes for murine embryonic development can demonstrate a disparate phenotype in human cohorts. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we discovered that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 resulted in non-human primate embryos which did not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos displayed a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirmed a similar role of ISL1 in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.

中文翻译：

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羊膜信号对于灵长类中胚层形成至关重要

鼠胚胎发育的必需基因可以在人类队列中表现出完全不同的表型。通过从植入后的非人类灵长类动物胚胎生成包含> 30,000个细胞的转录图集，我们发现ISL1（在心脏发生中具有公认作用的基因）控制着灵长类羊膜中的基因调控网络。靶向ISL1的CRISPR / Cas9产生了非人类的灵长类胚胎，该胚胎没有产生可存活的后代，这表明ISL1在灵长类动物胚胎发生中至关重要。在细胞水平上，由于来自羊膜的BMP4信号减少，突变的ISL1胚胎显示中胚层形成失败。通过功能丧失和人类胚胎干细胞的拯救研究，我们证实了ISL1在人类体外衍生羊膜中的相似作用。