Granulocyte colony-stimulating factor stimulates neurogenesis via vascular endothelial growth factor with STAT activation

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.