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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3757-3762
HEMATOPOIESIS
Hematopoietic stem cells express Tie-2 receptor in the murine
fetal liver
Hsiang-Chun Hsu,
Hideo Ema,
Mitsujiro Osawa,
Yukio Nakamura,
Toshio Suda, and
Hiromitsu Nakauchi
From the Department of Immunology, Institute of Basic
Medical Sciences, University of Tsukuba and Core Research for
Evolutional Science and Technology (Japan Science and Technology
Corporation), Tsukuba; and the Department of Cell Differentiation,
Institute of Molecular Embryology and Genetics, Kumamoto University
School of Medicine, Kumamoto, Japan.
Tie-2 receptor tyrosine kinase expressed in endothelial and
hematopoietic cells is believed to play a role in both angiogenesis and
hematopoiesis during development of the mouse embryo. This article
addressed whether Tie-2 is expressed on fetal liver hematopoietic stem
cells (HSCs) at day 14 of gestation. With the use of anti-Tie-2 monoclonal antibody, its expression was detected in approximately 7%
of an HSC population of Kit-positive, Sca-1-positive, lineage-negative or -low, and AA4.1-positive (KSLA) cells. These Tie-2-positive KSLA
(T+ KSLA) cells represent 0.01% to 0.02% of fetal liver
cells. In vitro colony and in vivo competitive repopulation assays were performed for T+ KSLA cells and Tie-2-negative KSLA
(T KSLA) cells. In the presence of stem cell factor,
interleukin-3, and erythropoietin, 80% of T+ KSLA cells
formed colonies in vitro, compared with 40% of T KSLA
cells. Long-term multilineage repopulating cells were detected in
T+ KSLA cells, but not in T KSLA cells. An in
vivo limiting dilution analysis revealed that at least 1 of 8 T+ KSLA cells were such repopulating cells. The successful
secondary transplantation initiated with a limited number of
T+ KSLA cells suggests that these cells have self-renewal
potential. In addition, engraftment of T+ KSLA cells in
conditioned newborn mice indicates that these HSCs can be adapted
equally by the adult and newborn hematopoietic environments. The data
suggest that T+ KSLA cells represent HSCs in the murine
fetal liver.
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