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 marrow CD34(+) cells. CD34(high)CD38(low)Thy1(+) 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, CD9(high)CD41(neg) 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 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 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. (Blood. 2001;97:1982-1989)
Clay
D
D
INSERM U268, Institut André LWOFF, Hôpital Paul Brousse, Villejuif, France.
Rubinstein
E
E
Mishal
Z
Z
Anjo
A
A
Prenant
M
M
Jasmin
C
C
Boucheix
C
C
Le Bousse-Kerdilès
M C
MC
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002462:Cell Membrane / Q000276:immunology / Q000648:ultrastructure; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016130:Immunophenotyping; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008562:Membrane Glycoproteins; D008854:Microscopy, Electron; D009244:NAD+ Nucleosidase / Q000096:biosynthesis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis; D060245:Tetraspanin 29
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D060245:Tetraspanin 29; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1