Distinct Repopulation Activity in Hu-Mice between CB- and LPB-CD34(＋) Cells by Enrichment of Transcription Factors

BACKGROUND AND OBJECTIVES: Human CD34(＋) hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)- and cord blood (CB)-derived CD34(＋) cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34(＋) cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34(＋) cells. Modeling the human hematolymphoid system is vital for studying immune cell crosstalk in human xenografted mice, with CB-CD34(＋) cells used as an optimized cell source because they are essential in reconstituting lymphoid lineage cells. METHODS AND RESULTS: In this study, we established hu-mice that combined human characteristics with long-term survival and investigated the efficiency of the engraftment of lymphoid lineage cells derived from LPB- and CB-CD34(＋) cells in the bone marrow, spleen, and LPB. We found an overall increase in the transcriptional activity of lymphoid lineage genes in CB-CD34(＋) cells. Our results revealed that potent CB-CD34(＋) cells displaying a general upregulation of the expression of genes involved in lymphopoiesis could contribute to the hematolymphoid system in the humanized mice model with longevity. CONCLUSIONS: Our data suggest that humanized mouse model by usage of CB-CD34(＋) cells displaying high expression of TFs for lymphoid lineage cells can contribute to study the immune response against lymphocytes.