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

• Published in: Neuroscience letters Vol. 476; no. 2; pp. 74 - 78
• Main Authors: Wang, Yang, Guan, Yunqian, Wang, Fang, Huang, Aihua, Wang, Shuyan, Zhang, Y. Alex
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 31.05.2010; Elsevier
• Subjects: Biological and medical sciences; Cell Line; Cell Proliferation; Cell Survival; Cellular Senescence; Cerebral Cortex - cytology; Fetus; Fundamental and applied biological sciences. Psychology; Humans; Ink4a/Arf locus; Lentivirus - genetics; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Over-expression; p16 Ink4a/p14 ARF; Polycomb Repressive Complex 1; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Repressor Proteins - physiology; RNA Interference; ShRNA; Stem Cells - cytology; Vertebrates: nervous system and sense organs; ShRNA; Ink4a/Arf locus; p16 Ink4a/p14 ARF; Over-expression; Human; Cell proliferation; Senescence; p14; p16; Stem cell; Gene overexpression; Fetus; In vitro
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.04.006

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.