Mouse embryonic stem cells (mESCs) are key components in generating mouse models for human diseases and performing basic research on pluripotency, yet the number of genes essential for mESCs is still unknown. We performed a genome-wide screen for essential genes in mESCs and compared it to screens in human cells. We found that essential genes are enriched for basic cellular functions, are highly expressed in mESCs, and tend to lack paralog genes. We discovered that genes that are essential specifically in mESCs play a role in pathways associated with their pluripotent state. We show that 29.5% of human genes intolerant to loss-of-function mutations are essential in mouse or human ESCs, and that the human phenotypes most significantly associated with genes essential for ESCs are neurodevelopmental. Our results provide insights into essential genes in the mouse, the pathways which govern pluripotency, and suggest that many genes associated with neurodevelopmental disorders are essential at very early embryonic stages.

中文翻译：

---

胚胎干细胞必不可少的基因与神经发育障碍有关。

小鼠胚胎干细胞（mESCs）是产生人类疾病的小鼠模型并进行多能性基础研究的关键组成部分，但mESCs必需的基因数目仍然未知。我们对mESCs中的必需基因进行了全基因组筛选，并将其与人类细胞中的筛选进行了比较。我们发现必需基因丰富了基本的细胞功能，在mESCs中高度表达，并且往往缺乏旁系同源基因。我们发现，mESC中特有的必不可少的基因在与其多能状态相关的途径中起作用。我们显示不耐受功能丧失突变的人类基因的29.5％是小鼠或人类ESC必不可少的，并且与ESC必不可少的基因最相关的人类表型是神经发育。