Open AccessSphingosine‐1‐Phosphate Receptor‐3 Supports Hematopoietic Stem and Progenitor Cell Residence Within the Bone Marrow Niche
Author(s) -
Ogle Molly E.,
Olingy Claire E.,
Awojoodu Anthony O.,
Das Anusuya,
Ortiz Rafael A.,
Cheung Hoi Yin,
Botchwey Edward A.
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2556
Subject(s) - homing (biology) , biology , progenitor cell , haematopoiesis , microbiology and biotechnology , bone marrow , stem cell , cxcr4 , immunology , hematopoietic stem cell , inflammation , ecology , chemokine
A bstract 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. S tem C ells 2017;35:1040–1052