Transcriptional Profiling of Lineage Depleted Dek-KO Murine Bone Marrow Treated with Exogenous DEK

Nuclear protein DEK is an endogenous DNA-binding chromatin factor regulating hematopoiesis. DEK is one of only two known secreted nuclear chromatin factors, but whether and how extracellular DEK regulates hematopoiesis is not known. We demonstrate that extracellular DEK greatly enhances ex vivo expansion of cytokine-stimulated human and mouse hematopoietic stem cells, and regulates hematopoiesis in vivo and in vitro. These effects are mediated through chemokine receptor CXCR2 and heparan sulfate proteoglycans, and are associated with enhanced phosphorylation of ERK1/2, AKT and p38 MAPK. Thus, DEK acts as a hematopoietic cytokine, with potential for clinical applicability. Overall design: Examination of lineage-negative and lineage-positive DEK-KO bone marrow (BM) cells with and without exogenous DEK