Megakaryocytes are large, polyploid cells that reside in the bone marrow and produce platelets (also known as thrombocytes). Megakaryocytes express CD41 and CXCR4, and both megakaryocytes and platelets express Thrombopoietin Receptor (Tpo R). In response to Tpo R signaling, megakaryocytes differentiate from precursor cells, grow in size, and release platelets via a budding mechanism. High numbers of circulating platelets are thought to negatively regulate their own production by sequestering Thrombopoietin (Tpo). This results in reduced levels of free Tpo and prevents additional megakaryocyte activation. In addition, other cytokines, such as IL-11, regulate megakaryopoiesis and can rescue platelet production in animal models of thrombocytopenia.