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Publication : Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells.

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.
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