Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells

Katsuto Takenaka, Tatiana K. Prasolava, Jean C.Y. Wang, Steven M. Mortin-Toth, Sam Khalouei, Olga I. Gan, John E. Dick, Jayne S. Danska

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296 Citations (Scopus)

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-α 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.

Original languageEnglish
Pages (from-to)1313-1323
Number of pages11
JournalNature Immunology
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Takenaka, K., Prasolava, T. K., Wang, J. C. Y., Mortin-Toth, S. M., Khalouei, S., Gan, O. I., Dick, J. E., & Danska, J. S. (2007). Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nature Immunology, 8(12), 1313-1323. https://doi.org/10.1038/ni1527