Comparison of the gene expression profiles of human hematopoietic stem cells between humans and a humanized xenograft model

The aim of this study is to evaluate the feasibility of NOD/Shi-scid-IL2Rγ^null (NOG) mice transplanted with human CD34⁺/CD38^-/Lin^-/low hematopoietic cells from cord blood (CB) as an experimental model of the gene expression in human hematopoiesis. We compared the gene expressions of human CD34⁺/CD38^-/Lin^-/low cells from human bone marrow (BM) and in xenograft models. The microarray data revealed that 25 KEGG pathways were extracted from the comparison of human CD34⁺/CD38^-/Lin^-/low HSCs between CB and BM, and that 17 of them—which were mostly related to cellular survival, RNA metabolism and lymphoid development—were shared with the xenograft model. When the probes that were commonly altered in CD34⁺/ CD38^-/Lin^-/low cells from both human and xenograft BM were analyzed, most of them, including the genes related hypoxia, hematopoietic differentiation, epigenetic modification, translation initiation, and RNA degradation, were downregulated. These alterations of gene expression suggest a reduced differentiation capacity and likely include key alterations of gene expression for settlement of CB CD34⁺/CD38^-/Lin^-/low cells in BM. Our findings demonstrate that the xenograft model of human CB CD34⁺/CD38^-/Lin^-/low cells using NOG mice was useful, at least in part, for the evaluation of the gene expression profile of human hematopoietic stem cells.