To stay or to leave: Stem cells and progenitor cells navigating the S1P gradient

Figure 2 Model of sphingosine-1-phosphate gradient in hematopoietic stem progenitor cell trafficking. A: Egression of hematopoietic stem progenitor cells (HSPCs) from bone marrow (BM) to peripheral blood. The molecular interactions of stromal cell-derived factor 1 (SDF-1)/CXCR4 and other adhesion molecules mediate the lodgment of HSPCs in BM niches. Blockage of the key retention signal SDF-1/CXCR4 with granulocyte colony-stimulating factor, Zymosan and CXCR4 antagonist AMD3100 promotes HSPC mobilization from bone morrow and release to peripheral blood. Eliminating sphingosine-1-phosphate (S1P) gradient either by charcoal stripping or blocking S1P lyase activity inhibits the HSPC mobilization to PB (pink-colored framed); B: Egression of HSPCs from tissue to lymph. HSPCs stay in tissue for a short time and then egress to lymph in response to S1P gradient. The disappearance of S1P gradient by the treatment of S1P lyase blocker THI causes the HSPCs be unable to enter lymph (pink-colored framed); C: Homing of HSPCs from blood to BM. FTY720 may promote primitive HSPC movement to BM through S1P₁ and S1P₅, or it may synergize with SDF-1/CXCR4 signaling for efficient HSPC homing and engraftment to BM. G-CSF: Granulocyte colony-stimulating factor.