Zinc finger E-box–binding homeobox 1 (ZEB1) is required for neural differentiation of human embryonic stem cells

Human pluripotent stem cells hold great promise for improving regenerative medicine. However, a risk for tumor formation and difficulties in generating large amounts of subtype derivatives remain the major obstacles for clinical applications of stem cells. Here, we discovered that zinc finger E-box–...

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Bibliographic Details
Published in:The Journal of biological chemistry 2018-12, Vol.293 (50), p.19317-19329
Main Authors: Jiang, Yuan, Yan, Long, Xia, Longkuo, Lu, Xiaoyin, Zhu, Wenliang, Ding, Dewen, Du, Mingxia, Zhang, Da, Wang, Hongmei, Hu, Baoyang
Format: Article
Language:English
Subjects:
adhesion
Animals
Brain - cytology
Cell Biology
Cell Differentiation
differentiation
embryonic stem cell
Gene Expression Regulation
Gene Knockout Techniques
Human Embryonic Stem Cells - cytology
Humans
Mice
neuron
Neurons - cytology
transplantation
ZEB1
Zinc Finger E-box-Binding Homeobox 1 - deficiency
Zinc Finger E-box-Binding Homeobox 1 - genetics
Zinc Finger E-box-Binding Homeobox 1 - metabolism
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Summary:Human pluripotent stem cells hold great promise for improving regenerative medicine. However, a risk for tumor formation and difficulties in generating large amounts of subtype derivatives remain the major obstacles for clinical applications of stem cells. Here, we discovered that zinc finger E-box–binding homeobox 1 (ZEB1) is highly expressed upon differentiation of human embryonic stem cells (hESCs) into neuronal precursors. CRISPR/Cas9-mediated ZEB1 depletion did not impede neural fate commitment, but prevented hESC-derived neural precursors from differentiating into neurons, indicating that ZEB1 is required for neuronal differentiation. ZEB1 overexpression not only expedited neural differentiation and neuronal maturation, which ensured safer neural cell transplantation, but also facilitated the generation of excitatory cortical neurons, which were valuable for managing certain neurological disorders, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Our study provides useful information on how human neural cells are generated, which may help in forming strategies for developing and improving replacement therapies for treating patients with neurological diseases.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA118.005498