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Nat Immunol. 2007 Dec;8(12):1313-23. Epub 2007 Nov 4.

Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells.

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  • 1Division of Cellular and Molecular Biology, University Health Network, Toronto, Ontario M5G2M9, Canada.

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-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.

PMID:
17982459
DOI:
10.1038/ni1527
[PubMed - indexed for MEDLINE]
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