Bmi1, medulloblastoma and regenerative therapy

The epigenetic gene regulator BMI1 induces neural stem cell self-renewal in vitro and in vivo, a function that could be useful in regenerative medicine. However, increased expression of BMI1 in medulloblastoma, a brain tumour that can arise from cerebellar granule cell progenitors (CGPs), suggests that BMI1 is oncogenic in some circumstances. Behesti et al. investigated this possibility by generating transgenic mice that overexpress Bmi1 in the granule cell lineage. Bmi1 overexpression in CGPs decreased cerebellar size by decreasing CGP proliferation, whereas its overexpression in postmitotic granule cells improved cell survival under stress. No medulloblastomas developed in the transgenic mice, but Bmi1 overexpression in a Trp53^−/− background produced a low incidence of medulloblastomas. Thus, BMI1 overexpression is not sufficient to induce neoplastic transformation but can improve neuronal survival under stress. These results have implications for regenerative therapies. Page 49