Sphingosine-1-Phosphate Receptor-3 Supports Hematopoietic Stem and Progenitor Cell Residence Within the Bone Marrow Niche
| Autor: | Molly E. Ogle, Hoi Yin Cheung, Anusuya Das, Rafael A. Ortiz, Anthony O. Awojoodu, Claire E. Olingy, Edward A. Botchwey |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Bone Marrow Cells Biology Ligands CXCR4 Article 03 medical and health sciences 0302 clinical medicine Sphingosine Radiation Ionizing Cell Adhesion medicine Animals Stem Cell Niche Progenitor cell Hematopoietic Stem Cell Mobilization S1PR3 Chemotaxis Hematopoietic Stem Cell Transplantation Cell Biology Hematopoietic Stem Cells Cell biology Mice Inbred C57BL Receptors Lysosphingolipid Haematopoiesis 030104 developmental biology medicine.anatomical_structure Cellular Microenvironment 030220 oncology & carcinogenesis Immunology Molecular Medicine Bone marrow Lysophospholipids Stem cell Developmental Biology Homing (hematopoietic) |
| Zdroj: | Stem Cells. 35:1040-1052 |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | Hematopoietic stem and progenitor cells (HSPCs) egress from bone marrow (BM) during homeostasis and at increased rates during stress; however, the mechanisms regulating their trafficking remain incompletely understood. Here we describe a novel role for lipid receptor, sphingosine-1-phosphate receptor 3 (S1PR3), in HSPC residence within the BM niche. HSPCs expressed increased levels of S1PR3 compared to differentiated BM cells. Pharmacological antagonism or knockout (KO) of S1PR3 mobilized HSPCs into blood circulation, suggesting that S1PR3 influences niche localization. S1PR3 antagonism suppressed BM and plasma SDF-1, enabling HSPCs to migrate toward S1P-rich plasma. Mobilization synergized with AMD3100-mediated antagonism of CXCR4, which tethers HSPCs in the niche, and recovered homing deficits of AMD3100-treated grafts. S1PR3 antagonism combined with AMD3100 improved re-engraftment and survival in lethally irradiated recipients. Our studies indicate that S1PR3 and CXCR4 signaling cooperate to maintain HSPCs within the niche under homeostasis. These results highlight an important role for S1PR3 in HSPC niche occupancy and trafficking that can be harnessed for both rapid clinical stem cell mobilization and re-engraftment strategies, as well as the opportunity to design novel therapeutics for control of recruitment, homing, and localization through bioactive lipid signaling. |
| Databáze: | OpenAIRE |
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