1. UTX Regulates Human Neural Differentiation and Dendritic Morphology by Resolving Bivalent Promoters
- Author
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Chang-Mei Liu, Ying-Ying Wang, Hong-Zhen Du, Zhao-Qian Teng, Qing Yuan Tang, Cong Liu, Shang-Kun Dai, and Shuang-Feng Zhang
- Subjects
0301 basic medicine ,Transcription, Genetic ,neural differentiation ,Human Embryonic Stem Cells ,Methylation ,Biochemistry ,Article ,Cell Line ,Histones ,03 medical and health sciences ,0302 clinical medicine ,UTX ,Neurites ,Genetics ,Humans ,CRISPR ,Cell Lineage ,Cell Self Renewal ,Promoter Regions, Genetic ,Gene ,Loss function ,Histone Demethylases ,Base Sequence ,biology ,Lysine ,Cell Differentiation ,Promoter ,Dendrites ,Cell Biology ,dendritic morphology ,Embryonic stem cell ,Neural stem cell ,Electrophysiological Phenomena ,Up-Regulation ,Cell biology ,030104 developmental biology ,biology.protein ,Demethylase ,bivalent promoters ,Neural development ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Summary 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., Graphical Abstract, Highlights • Loss of UTX in hESCs reduces their neural differentiation potential • The dendritic morphology of UTX KO neurons tends to be simplified • UTX regulates human neural development depending on its demethylation • UTX regulates the expression of genes by resolving bivalent promoters, In this article, Liu and colleagues show that the deletion of UTX in hESCs leads to the decline of their ability to differentiate into neurons, and the decrease of neurite complexity of neurons. UTX regulates dozens of genes involved in neural differentiation and synaptic function by resolving bivalent promoters depending on its demethylation.
- Published
- 2020
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