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Bmi-1 regulates self-renewal, proliferation and senescence of human fetal neural stem cells in vitro

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机构: [1]Cell Therapy Center, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China
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关键词: ShRNA Over-expression Ink4a/Arf locus p16(Ink4a)/p14(ARF)

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Knockout and knockdown studies have shown that the polycomb gene Bmi-1 is important for mouse postnatal and prenatal neural stem cells (NSCs) self-renewal and proliferation. Different downstream targets of Bmi-1 gene have been identified in mouse, including Ink4a/Arf locus in adult NSCs and p21 gene in embryonic NSCs. However, little is known regarding the role of Bmi-1 in human NSCs. Here, using lentiviral-delivered shRNA knockdown and over-expression techniques, we examined whether Bmi-1 is required for the self-renewal and proliferation of human fetal NSCs (hfNSCs) in vitro. Our results showed that shRNA-mediated Bmi-1 reduction profoundly impaired hfNSCs self-renewal and proliferation, whereas Bmi-1 over-expression promoted hfNSCs self-renewal capacity. Interestingly, different from mouse embryonic NSCs. Bmi-1 repressed Ink4a/Arf locus instead of p21 gene in human fetal NSCs. Moreover, Bmi-1 knockdown induced obvious senescence phenotype in hfNSCs. Further studies on the Bmi-1 pathways would help to understand the molecular mechanisms underlying hfNSCs self-renewal and human brain development. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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出版当年[2009]版:
大类 | 3 区 医学
小类 | 4 区 神经科学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
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出版当年[2008]版:
Q3 NEUROSCIENCES
最新[2023]版:
Q3 NEUROSCIENCES

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第一作者机构: [1]Cell Therapy Center, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China
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通讯机构: [1]Cell Therapy Center, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China
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