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    FGF2 and insulin signaling converge to regulate cyclin D expression in multipotent neural stem cells

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    Authors
    Adepoju, Adedamola
    Micali, Nicola
    Ogawa, Kazuya
    Hoeppner, Daniel J.
    McKay, Ronald D.G.
    Faculty Advisor
    Dan Hoeppner, MD (Johns Hopkins Medical School, Lieber Institute for Brain Development)
    UMass Chan Affiliations
    School of Medicine
    Document Type
    Journal Article
    Publication Date
    2014-03-01
    Keywords
    Animals
    Cell Proliferation
    Cyclin D
    DNA
    Female
    Fibroblast Growth Factor 2
    Insulin
    Intracellular Space
    Mice
    Mice, Inbred C57BL
    Models, Biological
    Multipotent Stem Cells
    Neural Stem Cells
    Protein Biosynthesis
    Proto-Oncogene Proteins c-fos
    Proto-Oncogene Proteins c-jun
    Signal Transduction
    Transcription, Genetic
    Cell Biology
    Developmental Biology
    Developmental Neuroscience
    Molecular and Cellular Neuroscience
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    Link to Full Text
    http://dx.doi.org/10.1002/stem.1575
    Abstract
    The ex vivo expansion of stem cells is making major contribution to biomedical research. The multipotent nature of neural precursors acutely isolated from the developing central nervous system has been established in a series of studies. Understanding the mechanisms regulating cell expansion in tissue culture would support their expanded use either in cell therapies or to define disease mechanisms. Basic fibroblast growth factor (FGF2) and insulin, ligands for tyrosine kinase receptors, are sufficient to sustain neural stem cells (NSCs) in culture. Interestingly, real-time imaging shows that these cells become multipotent every time they are passaged. Here, we analyze the role of FGF2 and insulin in the brief period when multipotent cells are present. FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c-Fos and c-Jun that lead to elevated cyclin D mRNA levels. Insulin signals through the PI3k/Akt pathway to regulate cyclins at the post-transcriptional level. This precise Boolean regulation extends our understanding of the proliferation of multipotent NSCs and provides a basis for further analysis of proliferation control in the cell states defined by real-time mapping of the cell lineages that form the central nervous system.
    Source
    Stem Cells. 2014 Mar;32(3):770-8. doi: 10.1002/stem.1575. Link to article on publisher's site
    DOI
    10.1002/stem.1575
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/49258
    PubMed ID
    24155149
    Notes

    Medical student Adedamola Adepoju participated in this study as part of the Senior Scholars research program at the University of Massachusetts Medical School.

    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/stem.1575
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    Senior Scholars Program

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