Stem cells persist throughout life by self-renewing in numerous tissues 
including the central and peripheral nervous systems. This raises the issue of 
whether there is a conserved mechanism to effect self-renewing divisions. 
Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to 
progressive postnatal growth retardation and neurological defects. Here we show 
that Bmi-1 is required for the self-renewal of stem cells in the peripheral and 
central nervous systems but not for their survival or differentiation. The 
reduced self-renewal of Bmi-1-deficient neural stem cells leads to their 
postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase 
inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate 
of proliferation. p16Ink4a deficiency partially reverses the self-renewal defect 
in Bmi-1-/- neural stem cells. This conserved requirement for Bmi-1 to promote 
self-renewal and to repress p16Ink4a expression suggests that a common mechanism 
regulates the self-renewal and postnatal persistence of diverse types of stem 
cell. Restricted neural progenitors from the gut and forebrain proliferate 
normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell 
self-renewal from restricted progenitor proliferation in these tissues.