Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells
Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells
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DOI：
10.1038/ni1527
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发表时间：
2007-12-01
影响因子：
30.5
通讯作者：
Danska, Jayne S.
中科院分区：
文献类型：
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作者：
Takenaka, Katsuto;Prasolava, Tatiana K.;Danska, Jayne S.
尽管人类白细胞抗原的供宿主遗传特性相同，但造血干细胞移植中的移植物失败仍会发生，这表明有其他因素调节移植物。在非糖尿病(NOD) -严重联合免疫缺陷（SCID）异种移植模型中，我们发现NOD背景比其他具有相同免疫缺陷相关突变的菌株更能实现更好的造血植入。我们使用位置遗传学来表征这种菌株特异性的分子基础，并发现NOD Sirpa等位基因为人类造血提供支持。NOD sirp - α与人CD47配体的结合增强，其在小鼠巨噬细胞上的表达是支持人造血所必需的。因此，我们已经确定Sirpa多态性是人类造血干细胞植入的一个强有力的遗传决定因素。
Graft failure in the transplantation of hematopoietic stem cells occurs despite donor-host genetic identity of human leukocyte antigens, suggesting that additional factors modulate engraftment. With the nobese diabetic ( NOD) -severe combined immunodeficiency ( SCID) xenotransplantation model, we found that the NOD background allowed better hematopoietic engraftment than did other strains with equivalent immunodeficiency-related mutations. We used positional genetics to characterize the molecular basis for this strain specificity and found that the NOD Sirpa allele conferred support for human hematopoiesis. NOD SIRP-alpha showed enhanced binding to the human CD47 ligand, and its expression on mouse macrophages was required for support of human hematopoiesis. Thus, we have identified Sirpa polymorphism as a potent genetic determinant of the engraftment of human hematopoietic stem cells.