Conditional Activation of Bmi1 Expression Regulates Self-renewal, Apoptosis, and Differentiation of Neural Stem/Progenitor Cells In Vitro and In Vivo.
In: Stem Cells, Jg. 29 (2011-04-01), Heft 4, S. 699-711
Online
academicJournal
Zugriff:
The Polycomb group protein Bmi1 is a key regulator of self-renewal of embryonic and adult central nervous system stem cells, and its overexpression has been shown to occur in several types of brain tumors. In a Cre/LoxP-based conditional transgenic mouse model, we show that fine-tuning of Bmi1 expression in embryonic neural stem cell (NSC) is sufficient to increase their proliferation and self-renewal potential both in vitro and in vivo. This is linked to downregulation of both the ink4a/ARF and the p21/Foxg1 axes. However, increased and ectopic proliferation induced by overexpression of Bmi1 in progenitors committed toward a neuronal lineage during embryonic cortical development, triggers apoptosis through a survivin-mediated mechanism and leads to reduced brain size. Postnatally, however, increased self-renewal capacity of neural stem/progenitor cells (NSPC) is independent of Foxg1 and resistance to apoptosis is observed in neural progenitors derived from NSC-overexpressing Bmi1. Neoplastic transformation is absent in mice-overexpressing Bmi1 aged up to 20 months. These studies provide strong evidence that fine tuning of Bmi1 expression is a viable tool to increase self-renewal capacity of NSCs both in vitro and in vivo without eliciting neoplastic transformation of these cells. S C 2011;29:700-712 [ABSTRACT FROM AUTHOR]
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Conditional Activation of Bmi1 Expression Regulates Self-renewal, Apoptosis, and Differentiation of Neural Stem/Progenitor Cells In Vitro and In Vivo.
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Autor/in / Beteiligte Person: | YADIRGI, GOKHAN ; LEINSTER, VERONICA ; ACQUATI, SERENA ; BHAGAT, HEETA ; SHAKHOVA, OLGA ; MARINO, SILVIA |
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Zeitschrift: | Stem Cells, Jg. 29 (2011-04-01), Heft 4, S. 699-711 |
Veröffentlichung: | 2011 |
Medientyp: | academicJournal |
ISSN: | 1066-5099 (print) |
DOI: | 10.1002/stem.614 |
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