Abstract
The adult brain harbors multipotent stem cells, which reside in specialized niches that support self-renewal. Granulocyte colony-stimulating factor (G-CSF) induces bone marrow stem cells proliferation and mobilization from their niche, and activates endothelial cell proliferation, which might help to establish a vascular niche for neural stem cells (NSCs). Here, we show that G-CSF induced receptor-mediated proliferation and differentiation of neural precursors in human NSCs cultures and in adult rat brain in vivo. In human NSCs cultures, G-CSF activated STAT3 and 5, and increased VEGF and its receptor, VEGFR2 (Flk-1) expression, and VEGFR2 tyrosine kinase inhibitor blocked the neurogenesis stimulated by G-CSF. G-CSF also activated endothelial cell proliferation in adult rat brain in vivo. Our results indicate that G-CSF stimulates neurogenesis through reciprocal interaction with VEGF and STAT activation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Brain / cytology
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Bromodeoxyuridine
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Calbindins
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Cell Count / methods
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cell Survival / physiology
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Interactions
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Embryo, Mammalian
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Endothelial Cells / drug effects
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Enzyme-Linked Immunosorbent Assay / methods
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Granulocyte Colony-Stimulating Factor / pharmacology*
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Humans
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Immunohistochemistry / methods
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Indoles
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Laminin / metabolism
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Neurons / physiology*
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Receptors, Granulocyte Colony-Stimulating Factor / physiology
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S100 Calcium Binding Protein G / metabolism
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STAT Transcription Factors / metabolism*
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Statistics, Nonparametric
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Stem Cells / drug effects*
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Tubulin / metabolism
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Vascular Endothelial Growth Factor A / pharmacology
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Vascular Endothelial Growth Factor A / physiology*
Substances
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Calbindins
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Enzyme Inhibitors
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Indoles
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Laminin
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Receptors, Granulocyte Colony-Stimulating Factor
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S100 Calcium Binding Protein G
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STAT Transcription Factors
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Tubulin
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Vascular Endothelial Growth Factor A
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Granulocyte Colony-Stimulating Factor
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DAPI
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Bromodeoxyuridine