Recent identification of platelet/megakaryocyte-biased hematopoietic stem/repopulating cells requires revision of the intermediate pathway for megakaryopoiesis. Here, we show a unipotent megakaryopoietic pathway bypassing the bipotent megakaryocyte/erythroid progenitors (biEMPs). Cells purified from mouse bone marrow by CD42b (GPIba) marking were demonstrated to be unipotent megakaryocytic progenitors (MKPs) by culture and transplantation. A subpopulation of freshly isolated CD411 cells in the lineage Sca1 1 cKit 1 (LSK) fraction (subCD41 1 LSK) differentiated only into MKP and mature megakaryocytes in culture. Although CD411 LSK cells as a whole were capable of differentiating into all myeloid and lymphoid cells in vivo, they produced unipotent MKP, mature megakaryocytes, and platelets in vitro and in vivo much more efficiently than Flt3 1 CD41 2 LSK cells, especially at the early phase after transplantation. In single cell polymerase chain reaction and thrombopoietin (TPO) signaling analyses, the MKP and a fraction of CD41 1 LSK, but not the biEMP, showed the similarities in mRNA expression profile and visible TPO-mediated phosphorylation. On increased demand of platelet production after 5-FU treatment, a part of CD41 1 LSK population expressed CD42b on the surface, and 90% of them showed unipotent megakaryopoietic capacity in single cell culture and predominantly produced platelets in vivo at the early phase after transplantation. These results suggest that the CD41 1 CD42b 1 LSK are straightforward progenies of megakaryocytes/plateletbiased stem/repopulating cells, but not progenies of biEMP. Consequently, we show a unipotent/highly biased megakaryopoietic pathway interconnecting stem/repopulating cells and mature megakaryocytes, the one that may play physiologic roles especially in emergency megakaryopoiesis.

The present study clearly shows that ET-1 and STX induce the histamine release from WP bodies of the toad aortas by means of HPLC and immunoelectron microscopy. Histamine discharged from the WP bodies may be involved in the vasocontraction evoked by ET-1 and STX.

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In the rat hind limb bud aged between prenatal days 14 and 16, immunoreactions of fibronectin in the apical ectodermal ridge were localized on the plasma membranes of epidermal cells and cytoplasmic projections of the underlying mesenchymal cells, which are in contact with the basal lamina. Those of integrin alpha 3 and alpha 5 subunits also appeared on such areas. Definite immunoreactions of fibronectin and both integrin subunits were seen in cell to cell contact areas of mesenchymal cells which are associated with the marginal vein, or with each other forming solid cell cords, and appeared on the basal plasma membrane of endothelial cells of the growing capillaries arising from the marginal vein. These findings suggest that fibronectin may work as a ligand for alpha 3 beta 1 and/or alpha 5 beta 1 integrins expressed by the mesenchymal and vasoformative cells in developing limb bud.