Epigenetic modifications of hematopoietic differentiation are recapitulated in humanized mice

Transplantation of human hematopoietic stem cells into immunodeficient mice is a valuable technique to gain insight into stemness and hematopoietic development in an in vivo environment. In this study we analyzed if transplanted hematopoietic cells in humanized mice recapitulate epigenetic changes of normal hematopoietic development. Hematopoietic stem and progenitor cells (CD34+) were isolated from human umbilical cord blood (CB) and 50,000 cells were intravenously injected into five 7 to 9 week old KIT-deficient NOD/SCID Il2rg-/-KitW41/W41 (NSGW41). 19 weeks after transplantation bone marrow was harvested, sorted for hCD45+ cells, and DNA methylation profiles were analyzed with Infinium HumanMethylation450 BeadChips (Illumina). DNA methylation patterns of normal hematopoietic development are overall recapitulated in the xenogeneic microenvironment – particularly those of normal early B cell progenitor cells. DNA from sorted human CD45+ cells from bone marrow of five humanized mice was bisulfite converted and hybridized to the Illumina Infinium 450k Human Methylation BeadChip.