Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population

Authors

  • Claudio Giachino,

    1. Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
    2. Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany
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  • Onur Basak,

    1. Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany
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  • Sebastian Lugert,

    1. Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
    2. Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany
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  • Philip Knuckles,

    1. Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany
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  • Kirsten Obernier,

    1. Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
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  • Roberto Fiorelli,

    1. Institut für Hirnforschung, Universität Zürich, Zürich, Switzerland
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  • Stephan Frank,

    1. Division of Neuropathology, Institute of Pathology, University of Basel, Basel, Switzerland
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  • Olivier Raineteau,

    1. Institut für Hirnforschung, Universität Zürich, Zürich, Switzerland
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  • Arturo Alvarez-Buylla,

    1. Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA
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  • Verdon Taylor

    Corresponding author
    1. Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
    2. Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany
    • Correspondence: Verdon Taylor, Ph.D., Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland. Telephone: +41 616953091; Fax: +41 616953090; e-mail: verdon.taylor@unibas.ch

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Abstract

Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP+ NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP+ NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and subventricular progenitors in the fetal and postnatal human brain. Loss of BLBP+ stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging. Stem Cells 2014;32:70–84

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