UTX, a H3K27me3 demethylase, plays an important role in mouse brain development. However, so little is known about the function of UTX in human neural differentiation and dendritic morphology. In this study, we generated UTX-null human embryonic stem cells using CRISPR/Cas9, and differentiated them into neural progenitor cells and neurons to investigate the effects of UTX loss of function on human neural development. The results showed that the number of differentiated neurons significantly reduced after loss of UTX, and that the dendritic morphology of UTX KO neurons tended to be simplified. The electrophysiological recordings showed that most of the UTX KO neurons were immature. Finally, RNA sequencing identified dozens of differentially expressed genes involved in neural differentiation and synaptic function in UTX KO neurons and our results demonstrated that UTX regulated these critical genes by resolving bivalent promoters. In summary, we establish a reference for the important role of UTX in human neural differentiation and dendritic morphology.

UTX是一种H3K27me3脱甲基酶，在小鼠大脑发育中起着重要作用。然而，关于UTX在人类神经分化和树突形态学中的功能知之甚少。在这项研究中，我们使用CRISPR / Cas9生成了非UTX的人类胚胎干细胞，并将其分化为神经祖细胞和神经元，以研究UTX功能丧失对人类神经发育的影响。结果表明，UTX丢失后分化神经元的数量明显减少，UTX KO神经元的树突形态趋于简化。电生理记录表明，大多数UTXKO神经元未成熟。最后，RNA测序鉴定了数十种差异表达的基因，这些基因参与UTX KO神经元的神经分化和突触功能，我们的结果表明，UTX通过解析二价启动子来调节这些关键基因。总之，我们为UTX在人类神经分化和树突形态学中的重要作用建立了参考。