Scheme summarizing the roles of CD31 in megakaryocytopoiesis. CD31 regulates megakaryocytopoiesis in a hierarchic manner (panel A). At a very early stage of megakaryocytopoiesis, CD31 deficiency affects the stem cell niche and subsequent stem cell characteristics (panel B). There is an expanded hematopoietic LSK population and corresponding increased quiescent G₀ phase Lin⁻ cell pool in CD31KO marrow. Later, in the absence of CD31, immature megakaryocytes exhibit defects in translocating from the stromal cell niche to the vascular niche, which leads to the accumulation of megakaryocytes in BM. Although the short-term CFU assay suggests decreased functional progenitor cell (progenitor cells with short-term reconstituting capabilities, which represent relatively active cells) number in CD31KO BM, total CD41a⁺ cells and mature megakaryocytes were increased, which could be the combinatory effect of increased megakaryocytic progenitor cell number (most of them presumed to be quiescent cells with long-term reconstituting capabilities) and migration defects of megakaryocytes in CD31KO BM. Despite the reduction in platelet release caused by the decreased of association between CD31KO megakaryocytes and marrow sinusoidal vasculature, extramedullary splenic megakaryocytopoiesis is enhanced to generate a normal peripheral blood platelet number.