First Author | Takenaka K | Year | 2007 |
Journal | Nat Immunol | Volume | 8 |
Issue | 12 | Pages | 1313-23 |
PubMed ID | 17982459 | Mgi Jnum | J:127760 |
Mgi Id | MGI:3764783 | Doi | 10.1038/ni1527 |
Citation | Takenaka K, et al. (2007) Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol 8(12):1313-23 |
abstractText | 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. |