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Blood, Vol. 93 No. 8 (April 15), 1999:
pp. 2586-2594
Stromal Cell CD9 Regulates Differentiation of Hematopoietic
Stem/Progenitor Cells
Keisuke Aoyama,
Kenji Oritani,
Takafumi Yokota,
Jun Ishikawa,
Tetsuo Nishiura,
Kensuke Miyake,
Yuzuru Kanakura,
Yoshiaki Tomiyama,
Paul W. Kincade, and
Yuji Matsuzawa
From Second Department of Internal Medicine, Osaka University Medical
School, Osaka, Japan; Department of Immunology, Saga Medical School,
Saga, Japan; Department of Hematology and Oncology, Osaka University
Medical School, Osaka, Japan; and Oklahoma Medical Research Foundation,
Oklahoma City, OK.
CD9 belongs to the transmembrane 4 superfamily, and has been shown
to influence cell proliferation, motility, and adhesion. We show here
that ligation of CD9 modifies proliferation and/or differentiation of
hematopoietic stem/progenitors. Pluripotent EML-C1 hematopoietic cells
were cocultured with MS-5 stromal cells in the presence of KMC8.8, an
anti-CD9 antibody. Numbers of recovered EML-C1 cells were slightly
reduced and the antibody caused the hematopoietic cells to migrate
beneath the adherent stromal cell layer. Of particular interest, EML-C1
cells recovered from CD9-ligated cultures had undifferentiated
properties. Separate pretreatment of the two cell types with antibody
showed that stromal-cell CD9 mediated these responses. Spontaneous
expression of erythroid marker was completely blocked and there was a
shift towards undifferentiated clonogenic progenitors.
Immunoprecipitation studies showed that stromal-cell CD9 associates
with the  1 subunit of integrin, as well as a novel 100 kD protein.
Antibody cross-linking of cell surface CD9 increased the amount of 100 kD protein that was subsequently coprecipitated with CD9. These
observations show that stromal-cell CD9 influences physical
interactions with hematopoietic cells and may be one factor that
determines the degree of stem cell differentiation.
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