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Predominant expression of a receptor tyrosine kinase, TIE, in hematopoietic
stem cells and B cells
M Hashiyama, A Iwama, K Ohshiro, K Kurozumi, K Yasunaga, Y Shimizu, Y Masuho, I Matsuda, N Yamaguchi and T Suda
Department of Cell Differentiation, Institute of Molecular Embryology and
Genetics, Kumamoto University School of Medicine, Japan.
A receptor tyrosine kinase (RTK), TIE (tyrosine kinase that contains
immunoglobulin-like loops and epidermal growth factor [EGF] homology
domains), is expressed in vascular endothelial and hematopoietic cells. We
generated monoclonal antibodies (MoAbs) against the extracellular domain of
TIE and a polyclonal antibody against the TIE carboxyterminus and used them
to analyze expression of TIE in hematopoietic cells. Western blotting
detected two forms of TIE protein with a molecular mass of 135 and 130 kD
in hematopoietic and endothelial cells. Northern blotting analysis revealed
that TIE was expressed preferentially in undifferentiated cell lines,
especially when megakaryocytic, but not erythroid differentiation was
induced. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed
that TIE was predominantly expressed in the human hematopoietic progenitor
fraction, CD34+ cells. Fluorescence- activated cell sorting (FACS) showed
that 42% of CD34+ and 17% of KIT- positive (KIT+) cells were TIE-positive
(TIE+). The majority (81%) of the primitive hematopoietic stem cells,
CD34+CD38- cells, were TIE+. Assays of progenitor cells and long-term
culture-initiating cells (LTC- IC) showed that the TIE+ fraction contained
more primitive cells than the TIE- fraction. Some TIE+ cells were in the
CD34- fraction, which were CD19+ and CD20+ (B cells). These findings
indicate that TIE has a unique spectrum of expression in primitive
hematopoietic stem cells and B cells. Although its ligand has not been
identified, TIE and its ligand may establish a novel regulatory pathway not
only in early hematopoiesis, but also in the differentiation and/or
proliferation of B cells.
Volume 87,
Issue 1,
pp. 93-101,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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