Directed differentiation of hippocampal stem/progenitor cells in the adult brain

Abstract

The multipotency of adult CNS stem cells has been shown in vitro, but not in vivo. Progenitors in the adult hippocampal subgranular zone normally generate only granule neurons. Retrovirus-mediated expression of the transcription factor Ascl1, however, resulted in the generation of immature and mature oligodendrocytes, demonstrating the progenitors' latent multipotency. Adult neurogenesis is a lifelong feature of brain plasticity; however, the potency of adult neural stem/progenitor cells in vivo remains unclear. We found that retrovirus-mediated overexpression of a single gene, the bHLH transcription factor Ascl1, redirected the fate of the proliferating adult hippocampal stem/progenitor (AHP) progeny and lead to the exclusive generation of cells of the oligodendrocytic lineage at the expense of newborn neurons, demonstrating that AHPs in the adult mouse brain are not irrevocably specified in vivo. These data indicate that AHPs have substantial plasticity, which might have important implications for the potential use of endogenous AHPs in neurological disease.