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

Nature Neuroscience volume 11, pages 888–893 (2008)Cite this article

Abstract

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.

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Figure 1: Ectopic Ascl1 expression changes the fate of newborn cells in the adult dentate gyrus.
Figure 2: Ascl1-expressing newborn cells have features of myelinating oligodendrocytes.
Figure 3: Long-term survival and species consistency of Ascl1-expressing cells.
Figure 4: Progeny of Ascl1-overexpressing cells and cells born under control conditions share common AHPs.
Figure 5: Retroviral Dlx2 does not affect neuronal differentiation in the adult hippocampus.
Figure 6: Ascl1 is expressed in the adult SVZ and rostral migratory stream (RMS).
Figure 7: Context-dependent effects of Ascl1.

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Acknowledgements

We thank M.L. Gage for editing the manuscript. The study was supported by grants from the Deutsche Forschungsgemeinschaft (Je297/1-1), American Epilepsy Society, Swiss National Science Foundation (to S.J.), and the US National Institute on Aging, the US National Institute of Neurological Disorders and Stroke, the Lookout Fund, the Christopher and Dana Reeve Foundation, the Picower Foundation and Project ALS (to F.H.G.).

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Authors and Affiliations

  1. Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.,

    Sebastian Jessberger, Nicolas Toni, Gregory D Clemenson Jr, Jasodhara Ray & Fred H Gage

  2. Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology (ETH) Zurich, Schafmattstrasse 18, 8093 Zurich, Switzerland.,

    Sebastian Jessberger

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  1. Sebastian Jessberger
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Contributions

S.J. conceived and carried out the experiments, analyzed the data and wrote the manuscript. N.T. performed the electron microscopy experiment. G.D.C. participated in viral injections and histological procedures. J.R. provided the stem cell cultures. F.H.G. revised the manuscript, gave conceptual input and obtained financial support.

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Correspondence to Sebastian Jessberger or Fred H Gage.

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Jessberger, S., Toni, N., Clemenson Jr, G. et al. Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nat Neurosci 11, 888–893 (2008). https://doi.org/10.1038/nn.2148

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