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Publication : Tetraspanin CD82 regulates S1PR<sub>1</sub>-mediated hematopoietic stem and progenitor cell mobilization.

First Author  Saito-Reis CA Year  2021
Journal  Stem Cell Reports Volume  16
Issue  10 Pages  2422-2431
PubMed ID  34534447 Mgi Jnum  J:314202
Mgi Id  MGI:6788483 Doi  10.1016/j.stemcr.2021.08.009
Citation  Saito-Reis CA, et al. (2021) Tetraspanin CD82 regulates S1PR1-mediated hematopoietic stem and progenitor cell mobilization. Stem Cell Reports 16(10):2422-2431
abstractText  Hematopoietic stem and progenitor cell (HSPC) mobilization into the blood occurs under normal physiological conditions and is stimulated in the clinic to enable the isolation of HSPCs for transplantation therapies. In the present study, we identify the tetraspanin CD82 as a novel regulator of HSPC mobilization. Using a global CD82 knockout (CD82KO) mouse, we measure enhanced HSPC mobilization after granulocyte-colony stimulating factor (G-CSF) or AMD3100 treatment, which we find is promoted by increased surface expression of the sphingosine 1-phosphate receptor 1 (S1PR1) on CD82KO HSPCs. Additionally, we identify a disruption in S1PR1 internalization in CD82-deficient HSPCs, suggesting that CD82 plays a critical role in S1PR1 surface regulation. Finally, combining AMD3100 and anti-CD82 treatments, we detect enhanced mobilization of mouse HSPCs and human CD34+ cells in animal models. Together, these data provide evidence that CD82 is an important regulator of HSPC mobilization and suggests exploiting the CD82 scaffold as a therapeutic target to enhance stem cell isolation.
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