FGFR1 Is Required for and Elucidates Multiple Mechanisms of HSC Mobilization.

Abstract 2532

Poster Board II-509

Though fibroblast growth factor receptor 1 (FGFR1) is known to be expressed in hematopoietic stem cells (HSCs), and FGF ligands can support their in vitro culture, the function of FGFR1 in HSCs in vivo has not been elucidated. We examined mouse models in which Fgfr1 is conditionally deleted in adult hematopoietic tissues. While they exhibit normal hematopoiesis, FGFR1-null HSCs fail to mobilize to peripheral tissues in response to 5-fluorouracil (5FU) and AMD3100; however, they mobilize at levels similar to control animals when treated with granulocyte-colony stimulating factor (G-CSF). Further investigation revealed that FGFR1-null HSCs cannot migrate in response to the CXCR4 ligand SDF-1 in vitro, and after 5FU treatment they display diminished expression of CXCR4 in bone marrow at time points prior to mobilization. Additionally, HSCs lacking FGFR1 cannot be expanded in culture, indicating they bear proliferation defects. Together, these data support a novel role for FGFR1 in mobilization of HSCs and indicate that activation of FGF signaling may distinguish stress-responsive HSC mobilization from more physiologic mechanisms triggered by cytokines such as G-CSF.