Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo
| Autor: | Dafydd G. Thomas, Anna V. Molofsky, Toshihide Iwashita, Sean J. Morrison, Johanna Buchstaller, Shenghui He |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Neurogenesis
Subventricular zone Mice Transgenic Nerve Tissue Proteins Biology Article Central nervous system (CNS) Nestin Mice Intermediate Filament Proteins Transgenic mouse Neurosphere Proto-Oncogene Proteins medicine Animals Humans Bmi-1 Progenitor cell Molecular Biology Cells Cultured Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation Neurons Polycomb Repressive Complex 1 Stem cell Brain Neoplasms Stem Cells Brain Nuclear Proteins Cell Biology Glioma Neural stem cell Cell biology Neuroepithelial cell Mice Inbred C57BL Repressor Proteins medicine.anatomical_structure Cell Transformation Neoplastic Over-expression Immunology Tumorigenesis Glioblastoma Neuroglia Developmental Biology Adult stem cell Hydrocephalus |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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