He, S. et al. Bmi-1 over-expression in neural stem/progenitor cells increases proliferation and neurogenesis in culture but has little effect on these functions in vivo. Dev. Biol. 328, 257-272

Howard Hughes Medical Institute, Department of Internal Medicine, Center for Stem Cell Biology, University of Michigan, 5435 Life Sciences Institute, 210 Washtenaw Ave., Ann Arbor, MI 48109-2216, USA.
Developmental Biology (Impact Factor: 3.55). 02/2009; 328(2):257-72. DOI: 10.1016/j.ydbio.2009.01.020
Source: PubMed


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 p16(Ink4a) and p19(Arf) 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.

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    • "When the production of ROS/RNS exceeds the endogenous antioxidant buffering capacity, oxidative stress-induced cellular damage occurs. There is increasing evidence that oxidative stress level is elevated in diseases such as DMD and in normal aging (Fulle et al., 2004; Whitehead et al., 2006; Jackson, 2009; Cozzoli et al., 2011; Spassov et al., 2011). Bmi1 has an important role in mitochondrial function and redox homeostasis in thymocytes and in neurons (Liu et al., 2009; Abdouh et al., 2012); however, the mechanisms mediating this role of Bmi1 are currently unclear. "
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    • "Bmi-1 has been reported as an oncogene that controls cell proliferation and invasion (29). Furthermore, Bmi-1 is also involved in the self-renewal of cancer stem cells, which may result in tumor initiation (30,31). In the present study, Bmi-1 was found to be significantly overexpressed in the gastric cancer tissues and cell lines compared with the adjacent normal tissues and GES-1 normal gastric epithelial cells, respectively. "
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    • "However, some studies suggest that such high values of Bmi1 in several tumors are the result of other mutations: when tested in in vivo transgenic mice models (compared to in vitro models), Bmi1 was observed to have a low proliferative effect, a low effect on fetal and adult neurogenesis, and a low effect on glial differentiation. Furthermore, it did not result in an increased capacity for self-renewal and neurogenic potential [105]. "
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