Tetraspanin CD82 regulates S1PR 1 -mediated hematopoietic stem and progenitor cell mobilization

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 m...

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Bibliographic Details
Published in:Stem cell reports 2021-10, Vol.16 (10), p.2422
Main Authors: Saito-Reis, Chelsea A, Balise, Victoria D, Pascetti, Erica M, Jiminez, Magdalena, Gillette, Jennifer M
Format: Article
Language:English
Subjects:
Animals
Antigens, CD34 - metabolism
Gene Expression Regulation
Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - metabolism
Humans
Kangai-1 Protein - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction
Sphingosine-1-Phosphate Receptors - metabolism
Stem Cells - metabolism
Tetraspanins - physiology
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Summary: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 (S1PR ) on CD82KO HSPCs. Additionally, we identify a disruption in S1PR internalization in CD82-deficient HSPCs, suggesting that CD82 plays a critical role in S1PR 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.
ISSN:2213-6711