CD9 and megakaryocyte differentiation

AbstractIt is shown that the tetraspanin CD9 has a complex pattern of distribution in hematopoietic cells and is heterogeneously expressed on human bone marrow CD34+ cells. CD34highCD38lowThy1+ primitive progenitors are contained in the population with intermediate CD9 expression, thus suggesting that CD9 expression may precede CD38 appearance. Cell sorting shows that colony-forming unit (CFU)-GEMM and CFU-GM are present in high proportions in this fraction and in the fraction with the lowest CD9 expression. Cells with the highest level of CD9 are committed to the B-lymphoid or megakaryocytic (MK) lineages, as shown by the co-expression of either CD19 or CD41/GPIIb and by their strong potential to give rise to CFU-MK. In liquid cultures, CD9highCD41neg cells give rise to cells with high CD41 expression as early as 2 days, and this was delayed by at least 3 to 4 days for the CD9mid cells; few CD41high cells could be detected in the CD9lowcell culture, even after 6 days. Antibody ligation of cell surface CD9 increased the number of human CFU-MK progenitors and reduced the production of CD41+ megakaryocytic cells in liquid culture. This was associated with a decreased expression of MK differentiation antigens and with an alteration of the membrane structure of MK cells. Altogether these data show a precise regulation of CD9 during hematopoiesis and suggest a role for this molecule in megakaryocytic differentiation, possibly by participation in membrane remodeling.