Scheme of the proposed model. (A) Steady-state, the gradient of S1P between the PB and the BM facilitates progenitor egress via S1P₁ mediated SDF-1 release. (B) Rapid mobilization (AMD3100), progenitor cells express elevated levels of S1P₁ in the BM, which increases their mobilization via the S1P gradient toward the blood. In addition, S1P increases SDF-1 release from the BM to the PB, thus enhancing progenitor cell trafficking. (C) Prolonged mobilization (G-CSF), S1P levels are increased in the BM and PB along with augmentation of the S1P₁ expressing progenitor cells. Moreover, ROS signaling is increased by S1P and HGF²⁴  on primitive SKL cells, enhancing progenitor cell motility, and on BM stromal cells, inducing SDF-1 secretion and release. All these events facilitate progenitor cell mobilization.