UTX Regulates Human Neural Differentiation and Dendritic Morphology by Resolving Bivalent Promoters

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.