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

Abstract
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.
AuthorsYuan Jiang, Long Yan, Longkuo Xia, Xiaoyin Lu, Wenliang Zhu, Dewen Ding, Mingxia Du, Da Zhang, Hongmei Wang, Baoyang Hu
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 293 Issue 50 Pg. 19317-19329 (12 14 2018) ISSN: 1083-351X [Electronic] United States
PMID30337365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2018 Jiang et al.
Chemical References
  • Zinc Finger E-box-Binding Homeobox 1
Topics
  • Animals
  • Brain (cytology)
  • Cell Differentiation
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Human Embryonic Stem Cells (cytology)
  • Humans
  • Mice
  • Neurons (cytology)
  • Zinc Finger E-box-Binding Homeobox 1 (deficiency, genetics, metabolism)

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