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    Requirement for fibroblast growth factor receptor 1 in hematopoietic stem cells under stress but not during homeostasis

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    Ross_ku_0099D_11055_DATA_1.pdf (6.396Mb)
    Issue Date
    2010-07-23
    Author
    Ross, Jason Thomas
    Publisher
    University of Kansas
    Format
    117 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Pathology & Laboratory Medicine
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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    Abstract
    Fibroblast growth factor (FGF) signaling promotes hematopoietic stem cell (HSC) expansion in vitro; however, its in vivo function remains unknown. Conditional deletion of FGFR1, predominantly expressed in HSCs, did not affect homeostatic hematopoiesis, but led to defects in mobilization of HSCs in response to induced bone marrow damage. Mechanistically, loss of FGFR1 caused defective expression of CXCR4, a receptor for the chemoattractant SDF-1, in HSCs, as well as impaired migration in response to SDF-1 by in vitro assay. This is consistent with failure of HSC mobilization by disruption of SDF-1 sig-naling with AMD3100. Additionally, defects in proliferation of HSCs prior to bone mar-row egress, and subsequent extramedullary expansion of HSCs within the spleen was observed in vivo. In total, this dissertation has characterized a role for FGFR1 in the mobi-lization of HSCs in vivo and may represent a rarely engaged signaling program that pro-motes stress reponse and hematopoietic recovery.
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    http://hdl.handle.net/1808/6769
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    • KU Med Center Dissertations and Theses [148]
    • Dissertations [2980]

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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