Effect of Bmi1 over-expression on gene expression in adult and embryonic murine neural stem cells.

The ability of isolated neural stem cells (NSCs) to proliferate as neurospheres is indicative of their competence as stem cells, and depends critically on the polycomb group (PcG) member Bmi1: knockdown of Bmi1 results in defective proliferation and self-renewal of isolated NSCs, whereas overexpression of Bmi1 enhances these properties. Here we report genome-wide changes in gene expression in embryonic and adult NSCs (eNSCs and aNSCs) caused by overexpression of Bmi1. We find that genes whose expression is altered by perturbations in Bmi1 levels in NSCs are mostly distinct from those affected in other multipotent stem/progenitor cells, such as those from liver and lung, aside from a small core of common targets that is enriched for genes associated with cell migration and mobility. We also show that genes differing in expression between prospectively isolated quiescent and activated NSCs are not affected by Bmi1 overexpression. In contrast, a comparison of genes showing altered expression upon Bmi1 overexpression in eNSCs and in aNSCs reveals considerable overlap, in spite of their different provenances in the brain and their differing developmental programs.