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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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"Coordinating Hematopoietic Stem Cell Trafficking through Sphingosine-1-phosphate Receptor Signals"
Claire Segar - PhD candidate
Ed Botchwey, PhD - Advisor
Hematopoietic stem cells (HSCs) traffic from the bone marrow niche into peripheral blood and tissue compartments in response to injury and inflammation. Understanding the signaling mechanisms that govern this cell mobilization and homing is critical in the design of novel endogenous tissue engineering strategies. The bone marrow niche compartment is a complex and highly organized structure made up of multiple cell types, matrices, and soluble factors that maintain and control HSC fate in vivo. Lipid mediators such as sphingosine-1-phosphate (S1P) have recently become recognized for their essential roles in spatial guidance, signaling, and ability to modify the sensitivity to other chemokines and growth factors. Here, we investigate the role of S1P receptors in governing the trafficking of hematopoietic stem and progenitor cells. We demonstrate that pharmacological antagonism of S1P receptor 3 leads to the rapid and selective mobilization of HSCs into peripheral blood in mice. Additionally, signaling through S1P receptors within bone marrow stromal cell populations alters the gradient of stromal derived factor-1 (SDF-1) across the endothelium. In a mouse model of lethal irradiation, we show that mobilized cells are capable of long-term re-engraftment and multilineage differentiation. This work establishes a role for S1P receptors in facilitating the trafficking of hematopoietic cells through differential receptor expression, which can be harnessed to enhance stem cell mobilization and re-engraftment.
