title: Bmi-1 regulates self-renewal, proliferation and senescence of human fetal neural stem cells in vitro.
abstract: 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.
authors.affiliation: Cell Therapy Center, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Guan
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Aihua
authors.initials: A
authors.lastname: Huang
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wang
authors.forename: Y Alex
authors.initials: YA
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D002540:Cerebral Cortex / Q000166:cytology*; D005333:Fetus; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1