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学科主题基础医学
Regulatory Role of the JNK-STAT1/3 Signaling in Neuronal Differentiation of Cultured Mouse Embryonic Stem Cells
Wei, Zheng Zachory1,2; Yu, Shan Ping1,2; Lee, Jin Hwan1; Chen, Dongdong1,2; Taylor, Tammi M.1; Deveau, Todd Carter1; Yu, Albert Cheung Hoi3,4; Wei, Ling1,5
关键词Embryonic stem cell JNK STAT3 Neurite outgrowth Neuronal differentiation
刊名CELLULAR AND MOLECULAR NEUROBIOLOGY
2014-08-01
DOI10.1007/s10571-014-0067-4
34期:6页:881-893
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Neurosciences
研究领域[WOS]Cell Biology ; Neurosciences & Neurology
关键词[WOS]N-TERMINAL KINASE ; NEURITE OUTGROWTH ; HUMAN NEUROBLASTOMA ; SELF-RENEWAL ; JNK PATHWAY ; IN-VITRO ; GROWTH ; ACTIVATION ; PROLIFERATION ; SURVIVAL
英文摘要

Stem cell transplantation therapy has provided promising hope for the treatment of a variety of neurodegenerative disorders. Among challenges in developing disease-specific stem cell therapies, identification of key regulatory signals for neuronal differentiation is an essential and critical issue that remains to be resolved. Several lines of evidence suggest that JNK, also known as SAPK, is involved in neuronal differentiation and neural plasticity. It may also play a role in neurite outgrowth during neuronal development. In cultured mouse embryonic stem (ES) cells, we test the hypothesis that the JNK pathway is required for neuronal differentiation. After neural induction, the cells were plated and underwent differentiation for up to 5 days. Western blot analysis showed a dramatic increase in phosphorylated JNKs at 1-5 days after plating. The phosphorylation of JNK subsequently induced activation of STAT1 and STAT3 that lead to expressions of GAP-43, neurofilament, beta III-tubulin, and synaptophysin. NeuN-colabelled with DCX, a marker for neuroblast, was enhanced by JNK signaling. Neuronal differentiation of ES cells was attenuated by treatment with SP600125, which inhibited the JNK activation and decreased the activation of STAT1 and STAT3, and consequently suppressed the expressions of GAP-43, neurofilament, beta III-tubulin, and the secretion of VEGF. Data from immunocytochemistry indicated that the nuclear translocation of STAT3 was reduced, and neurites of ES-derived neurons were shorter after treatment with SP600125 compared with control cells. These results suggest that the JNK-STAT3 pathway is a key regulator required for early neuronal differentiation of mouse ES cells. Further investigation on expression of JNK isoforms showed that JNK-3 was significantly upregulated during the differentiation stage, while JNK-1 and JNK-2 levels decreased. Our study provided interesting information on JNK functions during ES cell neuronal differentiation.

语种英语
WOS记录号WOS:000339382500011
项目编号NS045810 ; NS057255 ; NS075338 ; 0840110N ; C06 RR015455 ; 12GRNT12060222
资助机构National Institutes of Health, USA ; American Heart Association ; VA national merit grant ; NIH from the Extramural Research Facilities Program of the National Center for Research Resources
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67472
专题北京大学基础医学院_神经生物学系
作者单位1.Emory Univ, Sch Med, Dept Anesthesiol, Atlanta, GA 30322 USA
2.Atlanta VA Med Ctr, Ctr Visual & Neurocognit Rehabil, Decatur, GA 30033 USA
3.Peking Univ, Sch Basic Med Sci, Neurosci Res Inst, Beijing 100191, Peoples R China
4.Peking Univ, Sch Basic Med Sci, Dept Neurobiol, Beijing 100191, Peoples R China
5.Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
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GB/T 7714
Wei, Zheng Zachory,Yu, Shan Ping,Lee, Jin Hwan,et al. Regulatory Role of the JNK-STAT1/3 Signaling in Neuronal Differentiation of Cultured Mouse Embryonic Stem Cells[J]. CELLULAR AND MOLECULAR NEUROBIOLOGY,2014,34(6):881-893.
APA Wei, Zheng Zachory.,Yu, Shan Ping.,Lee, Jin Hwan.,Chen, Dongdong.,Taylor, Tammi M..,...&Wei, Ling.(2014).Regulatory Role of the JNK-STAT1/3 Signaling in Neuronal Differentiation of Cultured Mouse Embryonic Stem Cells.CELLULAR AND MOLECULAR NEUROBIOLOGY,34(6),881-893.
MLA Wei, Zheng Zachory,et al."Regulatory Role of the JNK-STAT1/3 Signaling in Neuronal Differentiation of Cultured Mouse Embryonic Stem Cells".CELLULAR AND MOLECULAR NEUROBIOLOGY 34.6(2014):881-893.
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