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

Neurosci Lett. 2010 May 31;476(2):74-8. doi: 10.1016/j.neulet.2010.04.006. Epub 2010 Apr 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Cell Survival
  • Cellular Senescence
  • Cerebral Cortex / cytology*
  • Fetus
  • Humans
  • Lentivirus / genetics
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • RNA Interference
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Stem Cells / cytology*


  • BMI1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 1