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

Research output: Contribution to journalArticlepeer-review

385 Citations (Scopus)


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
Issue number12
Publication statusPublished - Dec 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells'. Together they form a unique fingerprint.

Cite this