Polycomb group proteins are essential regulators of stem cell function during 
embryonic development and in adult tissue homeostasis. Bmi1, a key component of 
the Polycomb Repressive Complex 1, is highly expressed in undifferentiated 
neural stem cells (NSC) as well as in several human cancers including high-grade 
gliomas--highly aggressive brain tumors. Using a conditional gene activation 
approach in mice, we show that overexpression of Bmi1 induces repressive 
epigenetic regulation of the promoter of Survivin, a well-characterized 
antiapoptotic protein. This phenomenon is cell type-specific and it leads to 
apoptotic death of progenitor cells exclusively upon commitment toward a 
neuronal fate. Moreover, we show that this is triggered by increased oxidative 
stress-induced DNA damage. In contrast, undifferentiated NSC as well as 
glioma-initiating cells display an open chromatin configuration at the Survivin 
promoter and do not undergo apoptotic death. These findings raise the 
possibility that normal and neoplastic stem cells depend on the same mechanism 
for surviving the hyperproliferative state induced by increased Bmi1 expression.