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

Stem Cell Reports
Qing-Yuan TangChang-Mei Liu

Abstract

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.

Citations

Sep 28, 2021·Frontiers in Cell and Developmental Biology·Yajing MengWei Jiang
Oct 12, 2021·Cellular and Molecular Life Sciences : CMLS·Lucas E Cabrera ZapataMaría Julia Cambiasso

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Datasets Mentioned

BETA
GSE152448

Methods Mentioned

BETA
PCR
Knockout
immunoprecipitation
ChIP-seq
RNA-seq
flow cytometry
protein assay

Software Mentioned

Fiji
GraphPad Prism
Clampfit
ChromHMM

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