CD9 and megakaryocyte differentiation

It is shown that the tetraspanin CD9 has a complex pattern of distribution in hematopoietic cells and is heterogeneously expressed on human bone marro w CD34(+) cells. CD34(high)CD38(low)Thy1(-) primitive progenitors are conta ined in the population with intermediate CD9 expression, thus suggesting th at CD9 expression may precede CD38 appearance. Cell sorting shows that colo ny-forming unit (CFU)-GEMM and CFU-GM are present in high proportions in th is 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/GPllb a nd by their strong potential to give rise to CFU-MK. In liquid cultures, CD 9(high)CD41(neg) cells give rise to cells with high CD41 expression as earl y as 2 days, and this was delayed by at least 3 to 4 days for the CD9(mid) cells; few CD41(high) cells could be detected in the CD9(low) cell culture, even after 6 days, Antibody ligation of cell surface CD9 increased the num ber of human CFU-MK progenitors and reduced the production of CD41(+) megak aryocytic cells in liquid culture. This was associated with a decreased exp ression of MK differentiation antigens and with an alteration of the membra ne structure of MK cells. Altogether these data show a precise regulation o f CD9 during hematopoiesis and suggest a role for this molecule in megakary ocytic differentiation, possibly by participation in membrane remodeling. ( Blood, 2001;97: 1982-1989) 2001 by The American Society of Hematology. (C) 2001 by The American Society of Hematology.