Thrombopoietin induces production of nucleated thrombocytes from liver cells in Xenopus laevis

The development of mammalian megakaryocytes (MKs) and platelets, which are thought to be absent in non-mammals, is primarily regulated by the thrombopoietin (TPO)/Mpl system. Although non-mammals possess nucleated thrombocytes instead of platelets, the features of nucleated thrombocyte progenitors remain to be clarified. Here, we provide the general features of TPO using Xenopus laevis TPO ( xl TPO). Hepatic and splenic cells were cultured in liquid suspension with recombinant xl TPO. These cells differentiated into large, round, polyploid CD41-expressing cells and were classified as X . laevis MKs, comparable to mammalian MKs. The subsequent culture of MKs after removal of xl TPO produced mature, spindle-shaped thrombocytes that were activated by thrombin, thereby altering their morphology. Xl TPO induced MKs in cultured hepatic cells for at least three weeks; however, this was not observed in splenic cells; this result demonstrates the origin of early haematopoietic progenitors in the liver rather than the spleen. Additionally, xl TPO enhanced viability of peripheral thrombocytes, indicating the xl TPO-Mpl pathway stimulates anti-apoptotic in peripheral thrombocytes. The development of thrombocytes from MKs via the TPO-Mpl system in X. laevis plays a crucial role in their development from MKs, comparable to mammalian thrombopoiesis. Thus, our results offer insight into the cellular evolution of platelets/MKs in vertebrates. (200/200).