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Blood, 1 April 2001, Vol. 97, No. 7, pp. 1982-1989
HEMATOPOIESIS
CD9 and megakaryocyte differentiation
Denis Clay,
Eric Rubinstein,
Zohair Mishal,
Aurora Anjo,
Michel Prenant,
Claude Jasmin,
Claude Boucheix, and
Marie-Caroline Le Bousse-Kerdilès
From INSERM U268 and Service Commun de
Cytométrie; Institut André LWOFF and Laboratoire de
Microscopie Electronique du service d'Anatomopathologie; Hôpital
Paul Brousse, Villejuif, France.
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.
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 CD9low
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.
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