UTX Regulates Human Neural Differentiation and Dendritic Morphology by Resolving Bivalent Promoters
UTX Regulates Human Neural Differentiation and Dendritic Morphology by Resolving Bivalent Promoters
复制标题
UTX 通过解析二价启动子调节人类神经分化和树突形态
DOI：
10.1016/j.stemcr.2020.06.015
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发表时间：
2020
影响因子：
5.9
通讯作者：
Liu Chang-Mei
中科院分区：
文献类型：
--
作者：
Tang Qing-Yuan;Zhang Shuang-Fen;Dai Shang-Ku;Liu Cong;Wang Ying-Ying;Du Hong-Zhen;Teng Zhao-Qian;Liu Chang-Mei
UTX是一种H3K27me3去甲基化酶，在小鼠大脑发育中起重要作用。然而，目前对futxin在人类神经分化和树突形态中的作用知之甚少。本研究利用CRISPR/Cas9技术，生成dutx缺失的人胚胎干细胞，并将其分化为神经祖细胞和神经元，研究futx功能缺失对人神经发育的影响。结果显示，futxko缺失后分化神经元数量明显减少，futxko神经元树突形态趋于简化。电生理记录显示，大部分utxko神经元未成熟。最后，RNA测序鉴定了数十个与utxko神经元神经分化和突触功能相关的差异表达基因，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。综上所述，我们为futxin在人类神经分化和树突形态中的重要作用建立了参考。
UTX, a H3K27me3 demethylase, plays an important role in mouse brain development. However, so little is known about the function ofUTXin human neural differentiation and dendritic morphology. In this study, we generatedUTX-null human embryonic stem cells using CRISPR/Cas9, and differentiated them into neural progenitor cells and neurons to investigate the effects ofUTXloss of function on human neural development. The results showed that the number of differentiated neurons significantly reduced after loss ofUTX, and that the dendritic morphology ofUTXKO neurons tended to be simplified. The electrophysiological recordings showed that most of theUTXKO neurons were immature. Finally, RNA sequencing identified dozens of differentially expressed genes involved in neural differentiation and synaptic function inUTXKO neurons and our results demonstrated thatUTXregulated these critical genes by resolving bivalent promoters. In summary, we establish a reference for the important role ofUTXin human neural differentiation and dendritic morphology.