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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.

Multipotent neural stem cells (NSCs) can be isolated from various regions of the adult brain and propagated in vitro. Recent reports have suggested spontaneous fusion events among NSCs when grown as free-floating neurospheres that may affect the genetic composition of NSC cultures. We used adult NSCs expressing either red fluorescent protein (RFP) or green fluorescent protein (GFP) to analyze the fusion frequency of rat and mouse NSCs. Fluorescence-activated cell sorting (FACS) revealed that, under proliferating conditions, approximately 0.2% of rat and mouse NSCs coexpressed RFP and GFP irrespective of whether the cells were grown as neurospheres (mouse NSCs) or as attached monolayers (rat and mouse NSCs). Fused cells did not proliferate and could not be propagated, suggesting that aberrantly fused cells are not viable. Furthermore, we found that neither neurospheres nor monolayers grew clonally, because even very low-density cultures had spheres containing both GFP- and RFP-expressing cells and monolayer patches with GFP- and RFP-expressing cells in close proximity. The nonclonal growth between distinct NSC populations strongly suggests the use of careful and precise culture conditions, such as single-cell assays, to characterize potency and growth of NSCs in vitro.