以色列希伯来大学Nissim Benvenisty课题组利用单倍体人类胚胎干细胞的功能丧失筛选，绘制出胚层分化的必需基因回路图谱。该研究于2020年7月30日在线发表于国际学术期刊《细胞—干细胞》。

通过使用在单倍体人类多能干细胞（hPSC）中建立的全基因组功能丧失文库，研究人员绘制了人类多能干细胞（hPSC）分化为三个胚层的必需基因图谱。令人惊讶的是，研究人员观察到质膜相关重要基因的比例很高，这突出了每种谱系分化所需的信号通路。有趣的是，对所有遗传性神经系统疾病的分析发现，引起小头畸形的基因具有很高的必要性。

此外，研究人员展示了必需的转录因子以及分化为所有胚层所需的一组高尔基体和内质网相关基因之间的谱系特异性层次。这项工作通过定义特定胚层命运的重要驱动力和多能性退出的必需基因来揭示了调控人类早期原肠胚形成事件的基因网络。

据悉，多能干细胞可以分化为所有胚层，但是人类这些细胞命运转变所必需的基因仍然难以捉摸。

附：英文原文

Title: Mapping Gene Circuits Essential for Germ Layer Differentiation via Loss-of-Function Screens in Haploid Human Embryonic Stem Cells

Author: Atilgan Yilmaz, Carmel Braverman-Gross, Anna Bialer-Tsypin, Mordecai Peretz, Nissim Benvenisty

Issue&Volume: 2020-07-30

Abstract: Pluripotent stem cells can differentiate into all embryonic germ layers, yet the genesessential for these cell fate transitions in human remain elusive. Here, we mappedthe essential genes for the differentiation of human pluripotent stem cells (hPSCs)into the three germ layers by using a genome-wide loss-of-function library establishedin haploid hPSCs. Strikingly, we observed a high fraction of essential genes associatedwith plasma membrane, highlighting signaling pathways needed for each lineage differentiation.Interestingly, analysis of all hereditary neurological disorders uncovered high essentialityamong microcephaly-causing genes. Furthermore, we demonstrated lineage-specific hierarchiesamong essential transcription factors and a set of Golgi- and endoplasmic reticulum-relatedgenes needed for the differentiation into all germ layers. Our work sheds light onthe gene networks regulating early gastrulation events in human by defining essentialdrivers of specific embryonic germ layer fates and essential genes for the exit frompluripotency.

DOI: 10.1016/j.stem.2020.06.023

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30290-3