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Cellular and molecular characterization of the role of the flk-2/flt-3
receptor tyrosine kinase in hematopoietic stem cells
FC Zeigler, BD Bennett, CT Jordan, SD Spencer, S Baumhueter, KJ Carroll, J Hooley, K Bauer and W Matthews
Department of Molecular Biology, Cell Genetics, Genetech, Inc, South San
Francisco, CA.
The flk-2/flt-3 receptor tyrosine kinase was cloned from a hematopoietic
stem cell population and is considered to play a potential role in the
developmental fate of the stem cell. Using antibodies derived against the
extracellular domain of the receptor, we show that stem cells from both
murine fetal liver and bone marrow can express flk-2/flt-3. However, in
both these tissues, there are stem cell populations that do not express the
receptor. Cell cycle analysis shows that stem cells that do not express the
receptor have a greater percentage of the population in G0 when compared
with the flk-2/flt-3- positive population. Development of agonist
antibodies to the receptor shows a proliferative role for the receptor in
stem cell populations. Stimulation with an agonist antibody gives rise to
an expansion of both myeloid and lymphoid cells and this effect is enhanced
by the addition of kit ligand. These studies serve to further illustrate
the importance of the flk-2/flt-3 receptor in the regulation of the
hematopoietic stem cell.
Volume 84,
Issue 8,
pp. 2422-2430,
10/15/1994
Copyright © 1994 by The American Society of Hematology
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