Model of G-CSF–induced HPC mobilization. Osteoblasts constitutively produce large amounts of CXCL12, providing an important retention signal for HPCs in the bone marrow. G-CSF initiates the mobilization cascade by stimulating a population of G-CSFR+ cells in the bone marrow. These cells, in turn, negatively regulate osteoblast number and activity, resulting in decreased CXCL12 expression in the bone marrow. The consequent decrease in CXCR4 signaling in HPCs leads to their migration from the bone marrow to blood.