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Journal Article

Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population

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Giachino,  Claudio
Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Basak,  Onur
Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Lugert,  Sebastian
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Knuckles,  Philip
Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Taylor,  Verdon
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Giachino, C., Basak, O., Lugert, S., Knuckles, P., Obernier, K., Fiorelli, R., et al. (2013). Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population. Stem Cells, 32, 70-84.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-8925-A
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.