Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells

Nat Immunol. 2007 Dec;8(12):1313-23. doi: 10.1038/ni1527. Epub 2007 Nov 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / physiology*
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Polymorphism, Genetic*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*

Substances

  • Antigens, Differentiation
  • Receptors, Immunologic
  • SIRPA protein, human