Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells

被引：375

作者：

Takenaka, Katsuto

Prasolava, Tatiana K.

Wang, Jean C. Y.

Mortin-Toth, Steven M.

Khalouei, Sam

Gan, Olga I.

Dick, John E.

Danska, Jayne S.

机构：

[1] Hosp Sick Children, Res Inst, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada

[2] Univ Hlth Network, Div Cell & Mol Biol, Toronto, ON M5G 2M9, Canada

[3] Univ Toronto, Univ Hlth Network, Dept Med, Div Hematol & Med Oncol, Toronto, ON M5S 1A8, Canada

[4] Univ Toronto, Fac Med, Dept Mol Genet & Microbiol, Toronto, ON M5S 1A8, Canada

[5] Univ Toronto, Fac Med, Dept Immunol, Toronto, ON M5S 1A8, Canada

[6] Univ Toronto, Fac Med, Dept Med Biophys, Toronto, ON M5S 1A8, Canada

[7] Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON M5S 1A8, Canada

来源：

NATURE IMMUNOLOGY | 2007年 / 8卷 / 12期

关键词：

D O I：

10.1038/ni1527

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1313 / 1323

页数：11

共 51 条

[1] THE 1ST EXTERNAL DOMAIN OF THE NONOBESE DIABETIC MOUSE CLASS-II I-A BETA-CHAIN IS UNIQUE [J].