HOXB4 in Hematopoietic Stem Cell Regulation

摘要: HOXB4 overexpression has been previously shown to increase hematopoietic stem cell renewal and enhance murine HSC competitive repopulation without compromising differentiation or homeostatic regulation of pool size. However, recent studies on human have indicated that forced expression may dysregulate lymphoid myeloid differentiation. In this study the effects were examined distribution lineage specification expressing cells in a congenic assay. Retroviral (HSCs) resulted increased frequency long-term culture initiating (LTC-IC) vitro, indicative selective growth advantage but with no significant difference mean CFC/LTC-IC ratio, an indicator balanced Competitive vivo assays transplants different combinations HOXB4- GFP-transduced bone marrow showed engraftment transduced marrow, thymus, blood, spleen. Engraftment levels disproportionately high thymus relative spleen peripheral while multilineage analysis predominance lineages. Thymic revealed HOXB4-dependent thymic size due numbers mature CD4 CD8 T consistent abnormality release lymphocytes from abnormalities persisted secondary transplants. These results support potential alter balance hematopoiesis suggest fundamental alterations induced by T-cell trafficking. emphasize need for careful evaluation clinical gene therapy applications HOXB4.