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

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.