Directing neurotransmitter identity of neurones derived from expanded adult neural stem cells

Authors

  • Benedikt Berninger,

    1. Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Schillerstrasse 46, D-80336 Munich, Germany
    2. Institute for Stem Cell Research, National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany
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  • François Guillemot,

    1. National Institute for Medical Research, Division of Molecular Neurobiology, Mill Hill, London, UK
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  • Magdalena Götz

    1. Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Schillerstrasse 46, D-80336 Munich, Germany
    2. Institute for Stem Cell Research, National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany
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Dr Magdalena Götz, and Dr Benedikt Berninger 1Department of Physiological Genomics, as above.
E-mail: magdalena.goetz@gsf.de or benedikt.berninger@gsf.de

Abstract

In-vitro expanded neural stem cells (NSCs) of the adult subependymal zone (SEZ) may serve as a source for replacing degenerating neurones in disease and trauma. Crucial for the viability of this approach is the ability to selectively generate specific types of neurones from these cells. Here we show that NSCs derived from the adult mouse SEZ and expanded in vitro as neurosphere cells lose their in-vivo specification and generate a mixture of progeny comprising both GABAergic and also, surprisingly, glutamatergic neurones. When forced to express the pro-neural transcription factor neurogenin 2, virtually all progeny of in-vitro expanded adult NSCs acquire a glutamatergic identity, whereas only GABAergic neurones are generated upon expression of the transcription factor Mash1. Respecification of expanded NSCs from the adult SEZ by neurogenin 2 was accompanied by upregulation of the T-box transcription factor Tbr1, suggesting that their progeny had acquired a dorsal telencephalic identity. Thus, in-vitro expanded adult NSCs have the competence to become directed towards distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided.

Ancillary