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

转录因子富集导致人源小鼠 CB- 和 LPB-CD34+ 细胞的再生活性存在差异

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作者:A-Reum Han ,Jeong Eun Lee ,Min Ji Lee ,Seung Young Ko ,Hyun Soo Shin ,Ji Yoon Lee ,Dong Ryul Lee

Abstract

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.

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