Sphingosine-1-Phosphate Receptor-3 Supports Hematopoietic Stem and Progenitor Cell Residence Within the Bone Marrow Niche.

ABSTRACT: 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 de

SUBMITTER: Ogle ME 

PROVIDER: S-EPMC5367957 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature