Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells
| Autor: | John E. Dick, Sam Khalouei, Katsuto Takenaka, Jean C.Y. Wang, Steven M. Mortin-Toth, Jayne S. Danska, Tatiana K. Prasolava, Olga I. Gan |
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| Rok vydání: | 2007 |
| Předmět: |
Polymorphism
Genetic Xenotransplantation medicine.medical_treatment CD47 Immunology Hematopoietic Stem Cell Transplantation Human leukocyte antigen Nod Mice SCID Biology Hematopoietic Stem Cells Antigens Differentiation Transplantation Haematopoiesis Mice Mice Inbred NOD medicine Signal-regulatory protein alpha Immunology and Allergy Animals Humans Stem cell Receptors Immunologic |
| Zdroj: | Nature immunology. 8(12) |
| ISSN: | 1529-2916 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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