CD34 modulates the trafficking behavior of hematopoietic cells in vivo

The CD34 surface antigen has been recognized as a marker of hematopoietic stem cells (HSCs) and is widely used for HSC selection as well as for quality control in HSC transplantation. CD34 has been implicated in cytoadhesion signaling, and its expression has been suggested to reflect the activation state of hematopoietic progenitor cells. However, the function of CD34 remains essentially unknown. Here we analyzed the effects of ectopic CD34 expression in vivo in a bone marrow transplantation model. We transduced murine bone marrow stem cells with retroviral vectors encoding either murine full-length or the alternative splice product truncated CD34. Transduced cells were transplanted into syngeneic, marrow ablated hosts. For comparison, control animals received either enhanced green fluorescent protein (eGFP)-transduced or mock-transduced cells. Six months post-transplantation, transduced differentiated blood cells ectopically expressing murine CD34 showed decreased migration from peripheral blood to both bone marrow and thymus, an effect that was more pronounced with full-length CD34 than with the truncated variant. In contrast, no influence of transgene expression on trafficking of differentiated blood cells was seen in the eGFP control group. Our data indicate that CD34 expression in mature blood cells has a suppressive effect on cellular trafficking to hematopoietic stroma organs, thereby supporting a modulating role of the CD34 molecule in cytoadhesion.