Bmi-1基因对人类胚胎纹状体来源神经干细胞凋亡的影响

doi:10.3969/j.issn.1006-7795.2015.01.020

首都医科大学学报 ›› 2015, Vol. 36 ›› Issue (1): 103-110.doi: 10.3969/j.issn.1006-7795.2015.01.020

Bmi-1基因对人类胚胎纹状体来源神经干细胞凋亡的影响

赵春松^1,2, 邹海强³, 闫晓明⁴, 陈凌⁵, 王佳茵^1,2, 关云谦^1,2, 张愚^1,2

1. 首都医科大学宣武医院细胞生物室, 北京 100053;
2. 教育部神经变性病重点实验室, 北京 100053;
3. 广州军区广州总医院神经内科, 广州 510010;
4. 首都医科大学宣武医院功能神经外科, 北京 100053;
5. 首都医科大学宣武医院神经外科, 北京 100053

收稿日期:2014-09-11 出版日期:2015-02-21 发布日期:2015-01-31
通讯作者: 关云谦 E-mail:guanyunqian@aliyun.com
基金资助:
国家重点基础研究发展计划资助项目(973计划)(2012CBA01300);国家高技术研究发展计划资助项目(863计划)(2011AA020106);北京市自然科学基金(7102078);北京市科技新星项目(2009B22);北京市科委健康培育项目(Z111107067311033);北京市教育委员会科技计划重点项目(KZ201310025024).

Effect of Bmi-1 on apoptosis of human fetal striatum derived neural stem cells

Zhao Chunsong^1,2, Zou Haiqiang³, Yan Xiaoming⁴, Chen Ling⁵, Wang Jiayin^1,2, Guan Yunqian^1,2, Zhang Y. Alex^1,2

1. Department of Cell Biology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
2. Key Laboratory of Neurodegeneration, Ministry of Education, Beijing 100053, China;
3. Department of Neurology, The General Hospital of Guangzhou Military Command in Guangzhou, Guangzhou 510010, China;
4. Department of Function Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
5. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Received:2014-09-11 Online:2015-02-21 Published:2015-01-31
Supported by:
This study was supported by National Program on Key Basic Research Project (2012CBA01300);National High Technology Research and Development Program of China (2011AA020106); Natural Science Foundation of Beijing (7102078); Beijing Nova Program of Science and Technology (2009B22); Beijing Municipal Science and Technology Commission (Z111107067311033); Key Project of Beijing Municipal Education Commission Science and Technology Program(KZ201310025024).

摘要/Abstract

摘要： 目的探讨Bmi-1基因对人类胚胎纹状体来源神经干细胞(neural stem cell, NSC)凋亡的影响.方法提取16~18周自然流产胚胎脑组织纹状体的NSC,体外培养至3~5代,用慢病毒载体对其进行Bmi-1基因的RNA干扰和过表达回复.观察Bmi-1基因对体外NSC凋亡的影响.结果在感染后2 h和3 d两个时间点,Bmi-1基因的RNA干扰显著增加了体外培养的NSC的凋亡率.结论 Bmi-1基因对于体外培养的NSC具有抑制其凋亡的作用,在分析该基因对NSC增生、自我更新等生物学属性的影响时,应当将Bmi-1基因的抗凋亡作用考虑在内.

关键词: 神经干细胞, 凋亡, Bmi-1, 癌基因

Abstract: Objective To explore the effect of Bmi-1 on the apoptosis of human fetal striatum derived neural stem cell (NSC). Methods The NSC was isolated from the striatum of 16-18 week fetus suffered from accidental spontaneous abortion, cultured and passaged 3-5 times in vitro. Bmi-1RNA interference and rescue (over-expression of Bmi-1) experiments were performed by lentivirus. The effects of Bmi-1 on the apoptosis of NSC were then observed.Results The Bmi-1 transcription of human striatum derived NSCs was decreased significantly by RNAi and was reversed by rescue experiments(overexpression of Bmi-1). Correspondingly, both at the time points of 2h and 3d after passaging, the RNAi of Bmi-1 increased the apoptosis significantly. Conclusion Given human fetal striatum derived NSCs, Bmi-1 inhibited their apoptosis in vitro. In the cases studying the effect of Bmi-1 on the self-renewal, proliferation of NSC, the anti-apoptosis effect of Bmi-1 should be taken into consideration.

Key words: neural stem cell, apoptosis, Bmi-1, oncogene

中图分类号:

R392.2

赵春松, 邹海强, 闫晓明, 陈凌, 王佳茵, 关云谦, 张愚. Bmi-1基因对人类胚胎纹状体来源神经干细胞凋亡的影响[J]. 首都医科大学学报, 2015, 36(1): 103-110.

Zhao Chunsong, Zou Haiqiang, Yan Xiaoming, Chen Ling, Wang Jiayin, Guan Yunqian, Zhang Y. Alex. Effect of Bmi-1 on apoptosis of human fetal striatum derived neural stem cells[J]. Journal of Capital Medical University, 2015, 36(1): 103-110.

参考文献

[1] Gage F H. Mammalian neural stem cells[J]. Science, 2000, 287(5457): 1433-1438.
[2] Doetsch F, Alvarez-Buylla A. Network of tangential pathways for neuronal migration in adult mammalian brain[J]. Proc Natl Acad Sci USA, 1996, 93(25): 14895-14900.
[3] Schmidt-Hieber C, Jonas P, Bischofberger J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus[J]. Nature, 2004, 429(6988):184-187.
[4] Molofsky A V, Slutsky S G, Joseph N M,et al. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing[J]. Nature, 2006, 443(7110):448-452.
[5] Krishnamurthy J, Ramsey M R, Ligon K L, et al. p16INK4a induces an age-dependent decline in islet regenerative potential[J]. Nature, 2006, 443(7110):453-457.
[6] Janzen V, Forkert R, Fleming H E, et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a[J]. Nature, 2006, 443(7110): 421-426.
[7] Molofsky A V, Pardal R, Iwashita T, et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation[J]. Nature, 2003, 425(6961): 962-967.
[8] Wang Y, Guan Y, Wang F, et al. Bmi-1 regulates self-renewal, proliferation and senescence of human fetal neural stem cells in vitro[J]. Neurosci Lett, 2010, 476(2): 74-78.
[9] Zaidi H A, Kosztowski T, DiMeco F, et al. Origins and clinical implications of the brain tumor stem cell hypothesis[J]. J Neurooncol, 2009, 93(1): 49-60.
[10] Cui H, Hu B, Li T, et al. Bmi-1 is essential for the tumorigenicity of neuroblastoma cells[J]. Am J Pathol, 2007, 170(4): 1370-1378.
[11] Wiederschain D, Chen L, Johnson B, et al. Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis[J]. Mol Cell Biol, 2007, 27(13): 4968-4979.
[12] 张红,刘庆华,周丽,等. 骨髓增生异常综合征原癌基因Bmi-1表达的检测[J]. 中华肿瘤防治杂志, 2014,21(3):211-213.
[13] Wu Z, Min L, Chen D, et al. Overexpression of BMI-1 promotes cell growth and resistance to cisplatin treatment in osteosarcoma[J]. PLoS One, 2011, 6(2): e14648.
[14] Lee K, Adhikary G, Balasubramanian S, et al. Expression of Bmi-1 in epidermis enhances cell survival by altering cell cycle regulatory protein expression and inhibiting apoptosis[J]. J Invest Dermatol, 2008, 128(1): 9-17.
[15] Liu ZG, Liu L, Xu LH, et al. Bmi-1 induces radioresistance in MCF-7 mammary carcinoma cells[J]. Oncol Rep, 2012, 27(4): 1116-1122.
[16] Li J, Gong LY, Song LB, et al. Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-kappaB Pathway[J]. Am J Pathol, 2010, 176(2): 699-709.
[17] Jakob S, Corazza N, Diamantis E, et al. Detection of apoptosis in vivo using antibodies against caspase-induced neo-epitopes[J]. Methods, 2008, 44(3): 255-261.
[18] Boonman Z, Isacson O. Apoptosis in neuronal development and transplantation: role of caspases and trophic factors[J]. Exp Neurol, 1999, 156(1): 1-15.

Bmi-1基因对人类胚胎纹状体来源神经干细胞凋亡的影响

Effect of Bmi-1 on apoptosis of human fetal striatum derived neural stem cells

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