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Article

Loss of ZC4H2 and RNF220 Inhibits Neural Stem Cell Proliferation and Promotes Neuronal Differentiation

by 1,2,†, 2,3,†, 1,2, 1,2, 1, 2,3,4 and 1,5,*
1
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
2
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China
3
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, and KIZ – CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
4
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
5
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(7), 1600; https://doi.org/10.3390/cells9071600
Received: 29 May 2020 / Revised: 22 June 2020 / Accepted: 29 June 2020 / Published: 1 July 2020
(This article belongs to the Special Issue Neural Stem Cell Systems to Study Brain Development and Diseases)
The ubiquitin E3 ligase RNF220 and its co-factor ZC4H2 are required for multiple neural developmental processes through different targets, including spinal cord patterning and the development of the cerebellum and the locus coeruleus. Here, we explored the effects of loss of ZC4H2 and RNF220 on the proliferation and differentiation of neural stem cells (NSCs) derived from mouse embryonic cortex. We showed that loss of either ZC4H2 or RNF220 inhibits the proliferation and promotes the differentiation abilities of NSCs in vitro. RNA-Seq profiling revealed 132 and 433 differentially expressed genes in the ZC4H2−/− and RNF220−/− NSCs, compared to wild type (WT) NSCs, respectively. Specifically, Cend1, a key regulator of cell cycle exit and differentiation of neuronal precursors, was found to be upregulated in both ZC4H2−/− and RNF220−/− NSCs at the mRNA and protein levels. The targets of Cend1, such as CyclinD1, Notch1 and Hes1, were downregulated both in ZC4H2−/− and RNF220−/− NSCs, whereas p53 and p21 were elevated. ZC4H2−/− and RNF220−/− NSCs showed G0/G1 phase arrest compared to WT NSCs in cell cycle analysis. These results suggested that ZC4H2 and RNF220 are likely involved in the regulation of neural stem cell proliferation and differentiation through Cend1. View Full-Text
Keywords: ZC4H2; RNF220; neural stem cell; proliferation; differentiation; Cend1 ZC4H2; RNF220; neural stem cell; proliferation; differentiation; Cend1
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MDPI and ACS Style

Zhang, L.; Ye, M.; Zhu, L.; Cha, J.; Li, C.; Yao, Y.-G.; Mao, B. Loss of ZC4H2 and RNF220 Inhibits Neural Stem Cell Proliferation and Promotes Neuronal Differentiation. Cells 2020, 9, 1600. https://doi.org/10.3390/cells9071600

AMA Style

Zhang L, Ye M, Zhu L, Cha J, Li C, Yao Y-G, Mao B. Loss of ZC4H2 and RNF220 Inhibits Neural Stem Cell Proliferation and Promotes Neuronal Differentiation. Cells. 2020; 9(7):1600. https://doi.org/10.3390/cells9071600

Chicago/Turabian Style

Zhang, Longlong, Maosen Ye, Liang Zhu, Jingmei Cha, Chaocui Li, Yong-Gang Yao, and Bingyu Mao. 2020. "Loss of ZC4H2 and RNF220 Inhibits Neural Stem Cell Proliferation and Promotes Neuronal Differentiation" Cells 9, no. 7: 1600. https://doi.org/10.3390/cells9071600

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