B8: Role of NFAT Transcription Factors in Megakaryopoiesis

Project leader: PD Dr. A. Kiani

As precursors of peripheral blood platelets (thrombocytes), megakaryocytes play an important role for the regulation of coagulation, thrombosis and wound healing. Disorders of megakaryocyte function may lead to haematological diseases such as thrombocytopenia, myelofibrosis and leukemia. Megakaryocytes are a population of bone marrow cells which differentiate from hematopoietic stem cells under the influence of the cytokine thrombopoietin. This process of megakaryopoiesis lasts several days and is regulated by a complex interaction of various transcription factors (e.g. GATA-1, FOG).
The transcription factor NFAT (Nuclear Factor of Activated T cells) regulates the production of cytokines in activated T cells and is therefore of importance for the immune system. We have previously demonstrated that NFAT is also strongly expressed by bone marrow megakaryocytes, but the function of NFAT in these cells is unknown. The aim of the current project is to define the role of NFAT in megakaryopoiesis. For this purpose, we will use experimental systems in which the expression of NFAT is artificially either enhanced or suppressed. With these studies, we hope to obtain further insight into the molecular mechanisms regulating megakaryopoiesis. A better understanding of these processes may allow specific therapeutic interventions in megakaryocytic disorders in the future.