Abstract
Hematopoietic stem cell (HSC) transplantation is limited by histocompatibility barriers and by lack of space in bone marrow niches. These obstacles prevent in vivo analysis of histoincompatible mutant stem cells and of HSC functions in non-irradiated mice. By genetically combining immunodeficiency with impaired function of the growth factor receptor Kit in mice, we generated a 'universal' HSC recipient that efficiently accepts long-term histocompatible and histoincompatible HSCs without prior irradiation.
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Acknowledgements
We thank I. Horak (Leibniz Institute of Molecular Pharmacology, Berlin) and H.J. Fehling (Institute for Immunology, Ulm University) for providing Bclaf1-deficient and Mll5-deficient mice, respectively, G. Terszowski for help with flow cytometry and data analysis, S. Schlenner for help with bone marrow transplantations, and T. Feyerabend, C. Läufle and members of the animal facility for careful maintenance of mouse lines. H.-R.R. thanks S. Takeda for the original discussions on Kit compound-mutant mice. This work was supported by the Landesstiftung Baden-Württemberg (21-655.023/104) to C.W. and by the German Research Foundation (754-2-2) to H.-R.R.
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C.W. designed and performed research, analyzed data and wrote the paper. V.M. designed and performed research on Mll5−/− mutants. S.B. and C.C. performed research and R.B. provided crucial reagents. H.-R.R. designed research, analyzed data and wrote the paper.
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Supplementary Figures 1–4, Supplementary Table 1, Supplementary Results, Supplementary Discussion, Supplementary Methods (PDF 3813 kb)
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Waskow, C., Madan, V., Bartels, S. et al. Hematopoietic stem cell transplantation without irradiation. Nat Methods 6, 267–269 (2009). https://doi.org/10.1038/nmeth.1309
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DOI: https://doi.org/10.1038/nmeth.1309
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