Myb Regulation of Megakaryocyte Immune Differentiation

Abstract Recent publications have sparked a renewed interest towards the origin and functions of megakaryocytes localized to the lung. Our laboratory previously reported that lung and bone marrow megakaryocytes are morphologically and functionally distinct. Specifically, lung megakaryocytes are lower ploidy and more immune differentiated than bone marrow megakaryocytes. Despite these differences, however, we recently discovered that both megakaryocyte populations are derived from hematopoietic progenitors in the bone marrow. Consequently, we aim to determine the mechanistic determinants associated with differentiation of heterogenous megakaryocyte populations. My preliminary data identify the transcription factor Myb as a gene highly expressed in bone marrow, but not lung megakaryocytes. Using transgenic mouse models, I determined that Myb expressing megakaryocytes have decreased expression of immune markers. Furthermore, megakaryocyte specific deletion of Myb is associated with more immune differentiated megakaryocytes, representative of the subpopulation localized to the lung. We hypothesize that Myb limits megakaryocytes immune differentiation, and therefore regulates the function of lung versus bone marrow derived platelets. We seek to identify the mechanisms by which Myb regulates megakaryocyte immune differentiation to generate an expanded model of platelet function and phenotype. We seek to leverage this information to generate therapeutic strategies to target inflammation associated with cardiovascular disease pathologies.