Stem Cell and Regenerative Medicine

Multi-lineage neuronal, astrocytic and oligodendrocytic potential is a cardinal neural stem cell (NSC) trait. In the neurogenic zones of the adult mouse brain, NSCs in the sub-ventricular zone generate oligodendrocytes as well as neurons and astrocytes. In stark contrast, NSCs in the adult hippocampal dentate gyrus (DG) generate only granule neurons and astrocytes but never oligodendrocytes in vivo. It remains unclear how this cell fate restriction is controlled. Interestingly, DG NSCs also fail to generate oligodendrocytes in vitro suggesting that they have an intrinsic fate restriction. We have studied this fate restriction of DG NSCs and identified a novel cell intrinsic mechanism controlling NSC maintenance, neurogenesis and gliogenesis in the hippocampus in vivo and of DG NSCs in vitro. I will discuss our findings about how directed mRNA stability changes DG NSC fate and controls the production of oligodendrocytes. These findings have major implications not

only for the cell fate determination of NSCs and potentially other stem and progenitor cells outside the nervous system but also for therapeutic intervention for regulated cell replacement.