Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling

Authors

  • Jinqiao Sun,

    1. Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China
    2. Key Lab of Neonatal Disease, Ministry of Health, Shanghai, China
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    • Jinqiao Sun and Wenhao Zhou contributed equally to this work.

  • Wenhao Zhou,

    1. Key Lab of Neonatal Disease, Ministry of Health, Shanghai, China
    2. Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China
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    • Jinqiao Sun and Wenhao Zhou contributed equally to this work.

  • Duan Ma,

    1. Key Lab of Molecular Medicine, Ministry of Education, Shanghai Medical College
    2. Institutes of Biomedical Sciences, Fudan University, Shanghai, China
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  • Yi Yang

    Corresponding author
    1. Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, China
    2. Key Lab of Neonatal Disease, Ministry of Health, Shanghai, China
    • 399 Wanyuan Road, Shanghai 201102, China
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Abstract

To investigate whether and how endothelial cells affect neurogenesis, we established a system to co-culture endothelial cells and brain slices of neonatal rat and observed how subventricular zone cells differentiate in the presence of endothelial cells. In the presence of endothelial cells, neural stem cells increased in number, as did differentiated neurons and glia. The augmentation of neurogenesis was reversed by diminishing vascular endothelial growth factor (VEGF) expression in endothelial cells with RNA interference (RNAi). Microarray analysis indicated that expression levels of 112 genes were significantly altered by co-culture and that expression of 81 of the 112 genes recovered to normal levels following RNAi of VEGF in endothelial cells. Pathway mapping showed an enrichment of genes in the Notch and Pten pathways. These data indicate that endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF, possibly by activating the Notch and Pten pathways. Developmental Dynamics 239:2345–2353, 2010. © 2010 Wiley-Liss, Inc.

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