Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo

Shenghui He, Toshihide Iwashita, Johanna Buchstaller, Anna V. Molofsky, Dafydd Thomas, Sean J. Morrison

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The polycomb gene Bmi-1 is required for the self-renewal of stem cells from diverse tissues, including the central nervous system (CNS). Bmi-1 expression is elevated in most human gliomas, irrespective of grade, raising the question of whether Bmi-1 over-expression is sufficient to promote self-renewal or tumorigenesis by CNS stem/progenitor cells. To test this we generated Nestin-Bmi-1-GFP transgenic mice. Analysis of two independent lines with expression in the fetal and adult CNS demonstrated that transgenic neural stem cells formed larger colonies, more self-renewing divisions, and more neurons in culture. However, in vivo, Bmi-1 over-expression had little effect on CNS stem cell frequency, subventricular zone proliferation, olfactory bulb neurogenesis, or neurogenesis/gliogenesis during development. Bmi-1 transgenic mice were born with enlarged lateral ventricles and a minority developed idiopathic hydrocephalus as adults, but none of the transgenic mice formed detectable CNS tumors, even when aged. The more pronounced effects of Bmi-1 over-expression in culture were largely attributable to the attenuated induction of p16Ink4a and p19Arf in culture, proteins that are generally not expressed by neural stem/progenitor cells in young mice in vivo. Bmi-1 over-expression therefore has more pronounced effects in culture and does not appear to be sufficient to induce tumorigenesis in vivo.

Original languageEnglish (US)
Pages (from-to)257-272
Number of pages16
JournalDevelopmental Biology
Volume328
Issue number2
DOIs
StatePublished - Apr 15 2009

    Fingerprint

Keywords

  • Bmi-1
  • Central nervous system (CNS)
  • Glioblastoma
  • Glioma
  • Over-expression
  • Stem cell
  • Transgenic mouse
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this