机构：[a]Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing,首都医科大学宣武医院[b]Department of Neurosurgery, The Affiliated Hospital of Weifang Medical College, Weifang,[c]Department of Cell Biology, Xuanwu hospital of Capital Medical University, Beijing,首都医科大学宣武医院[d]Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing,神经外科首都医科大学宣武医院[e]Beijing Institute for Brain Disorders, Beijing, China
Background/Aims: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. Methods: We up-and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs. Results: Our results show that shRNA-mediated EphB4 reduction profoundly impaired hNSCs self-renewal and proliferation. Furthermore, detection of differentiation revealed that knockdown of EphB4 inhibited hNSCs differentiation towards a neuronal lineage and promoted hNSCs differentiation to glial cells. In contrast, EphB4 overexpression promoted hNSCs self-renewal and proliferation, further induced hNSCs differentiation towards a neuronal lineage and inhibited hNSCs differentiation to glial cells. Moreover, we found that EphB4 regulates cell proliferation mediated by the Abl-CyclinD1 pathway. Conclusion: These studies provide strong evidence that fine tuning of EphB4 expression is crucial for the proliferation and neuronal differentiation of hNSCs, suggesting that EphB4 might be an interesting target for overcoming some of the therapeutic limitations of neuronal loss in brain diseases. (C) 2017 The Author(s) Published by S. Karger AG, Basel
基金：
the National Science and Technology Major Project (2012ZX09102201-106)
the National Natural Science Foundation of China (81573633, 81503049, 81373994 and 81173575).
第一作者机构：[a]Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, Beijing,
通讯作者：
通讯机构：[*1]Department of Experimental Animal Center, Xuanwu Hospital of Capital Medical University, No. 45 Changchun Road, Xicheng District, Beijing, 100053, (China)[*2]Beijing Institute of Functional Neurosurgery, Xuanwu Hospital of Capital Medical University, No. 45 Changchun Road, Xicheng District, Beijing, 100053, (China)
推荐引用方式(GB/T 7714)：
Tingting Liu,Xianwei Zeng,Fangling Sun,et al.EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro[J].CELLULAR PHYSIOLOGY AND BIOCHEMISTRY.2017,41(2):819-834.doi:10.1159/000459693.
APA：
Tingting Liu,Xianwei Zeng,Fangling Sun,Hongli Hou,Yunqian Guan...&Wen Wang.(2017).EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,41,(2)
MLA：
Tingting Liu,et al."EphB4 Regulates Self-Renewal, Proliferation and Neuronal Differentiation of Human Embryonic Neural Stem Cells in Vitro".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 41..2(2017):819-834
