Nature Immunology：让移植更有效的基因-Sirpa基因
研究人员在11月在线出版的《自然—免疫学》（Nature Immunology）期刊上报告说，一种基因能够让小鼠更有效地接受人体骨髓细胞。这种名为Sirpa的基因限制了移植造血干细胞在移植过程中的失败，它是在研究不同免疫缺陷小鼠接受人体骨髓血干细胞的不同能力时被发现的。
对研究人类血细胞缺损或血细胞疾病来说，这是一种很有研究价值的小鼠。遗传关系很接近的小鼠品种在接受移植器官上表现了差异性，研究人员因此能很快缩小基因的搜寻范围。小鼠的Sirpa基因是多形态的，这意味着可以在这些基因中找到稳定的遗传差异性，并改变其功能。
Sirpa基因所编码的蛋白质被称为SIRP-阿尔法，它能与一种在人血细胞表面表达的CD47蛋白相互作用。这种相互作用被认为阻止了免疫清道夫噬菌细胞攻击和吃掉缺失CD47的细胞，或者是拥有CD47分子但不能被Sirpa基因识别的细胞。第二种可能性也许可以解释为什么部分小鼠拒绝人体血液的移植而别的小鼠却不会。
然而，这些差异性不仅仅局限于小鼠。人体Sirpa基因中也展示了同样的多态性。作者推测，这种差异性也许可以解释为什么有些捐赠者和接受者的组织类型匹配、但骨髓移植仍被拒绝的现象。如果这种推测正确，那么Sirpa基因就会成为鉴定捐赠者与接受者是否匹配的名单上的一员，从而让移植更安全、更成功。（科学时报）
原始出处:
Nature Immunology 8, 1313 - 1323 (2007)
Published online: 4 November 2007 | doi:10.1038/ni1527
Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells
Katsuto Takenaka1,6, Tatiana K Prasolava2,6, Jean C Y Wang1,3, Steven M Mortin-Toth2, Sam Khalouei2, Olga I Gan1, John E Dick1,4 & Jayne S Danska2,5
Abstract
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-
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.
- Division of Cellular and Molecular Biology, University Health Network, Toronto, Ontario M5G2M9, Canada.
- Program in Genetics and Genomic Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario M5G1X8, Canada.
- Division of Medical Oncology and Hematology, Department of Medicine, University Health Network, and Department of Medicine, University of Toronto, Toronto, Ontario M5S1A8, Canada.
- Department of Molecular Genetics and Microbiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S1A8, Canada.
- Departments of Immunology and Medical Biophysics and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S1A8, Canada.
- These authors contributed equally to this work.
Correspondence to: Jayne S Danska2,5 e-mail: jayne.danska@sickkids.ca
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