| 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 signaling with AMD3100. Additionally, defects in proliferation of HSCs prior to bone marrow 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 mobilization of HSCs in vivo and may represent a rarely engaged signaling program that promotes stress reponse and hematopoietic recovery. |
