Platelet Biogenesis

Approximately 750 billion platelets circulate in human blood, and 1011 platelets are produced daily in the human body to fulfill their physiological functions. The individual’s platelet count is maintained in a range of approximately 150.000-400.000 platelets per μL blood, ensured by a constant balance of platelet production and clearance.

Platelets are derived from megakaryocytes (MKs), which differentiate from hematopoietic stem cells (HSC). The process of platelet biogenesis in the bone marrow is unique in mammalian physiology. During their maturation, MKs become polyploid, markedly increase their size and form complex membrane invaginations termed demarcation membrane system (DMS), that serves as a membrane reservoir for the newly formed platelets. Mature MKs reside at vascular sinusoids where they form unidirectional long cytoplasmic extensions called proplatelets, which pass the endothelial barrier and are shed into the circulation, where the final sizing into hundreds of virtually identical platelets from a single MK takes place.

We have developed in vivo and ex vivo imaging approaches to study hematopoiesis in the bone marrow. Using these techniques, we could provide a revised model of thrombopoiesis challenging the previous model of megakaryocyte migration. Currently, we are investigating how megakaryocytes modulate hematopoiesis and the mobilization of bone marrow cells. Moreover, we study how chronic cardio-vascular diseases affect hematopoiesis and platelet biogenesis leading to altered platelet reactivity in thrombo-inflammatory processes.