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.

造血干细胞和祖细胞 (HSPC) 动员到血液中发生在正常生理条件下，并在临床上进行刺激，以便能够分离 HSPC 用于移植治疗。在本研究中，我们确定四跨膜蛋白 CD82 是 HSPC 动员的新型调节因子。使用全局 CD82 敲除 (CD82KO) 小鼠，我们测量了粒细胞集落刺激因子 (G-CSF) 或 AMD3100 治疗后 HSPC 动员的增强，我们发现这是通过鞘氨醇 1-磷酸受体 1 (S1PR 1) 表面表达的增加来促进_的）在 CD82KO HSPC 上。此外，我们发现CD82 缺陷的 HSPC 中S1PR ₁内化受到破坏，这表明 CD82 在 S1PR _{1中发挥着关键作用}表面调节。最后，结合 AMD3100 和抗 CD82 治疗，我们检测到动物模型中小鼠 HSPC 和人类 CD34+ 细胞的动员能力增强。总之，这些数据提供了 CD82 是 HSPC 动员的重要调节因子的证据，并建议利用 CD82 支架作为增强干细胞分离的治疗靶点。