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Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-05-1344.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 856-862
HEMATOPOIESIS
Hyaluronan is synthesized by primitive hemopoietic cells,
participates in their lodgment at the endosteum following
transplantation, and is involved in the regulation of their
proliferation and differentiation in vitro
Susan K. Nilsson,
David N. Haylock,
Hayley M. Johnston,
Teresa Occhiodoro,
Tracey J. Brown, and
Paul J. Simmons
From the Stem Cell Biology Laboratory, Peter MacCallum
Cancer Institute, Melbourne, Victoria, Australia; and the
Department of Biochemistry and Molecular Biology, Monash University,
Clayton, Australia.
The localization of adult hemopoiesis to the marrow involves
developmentally regulated interactions between hemopoietic stem cells
and the stromal cell-mediated hemopoietic microenvironment. Although
primitive hemopoietic cells exhibit a broad repertoire of
adhesion molecules, little is known about the molecules influencing the
site of cell lodgment within the marrow following
transplantation. However, our recent studies indicate that
hierarchically dependent patterns of migration of transplanted
hemopoietic cells result in the retention of primitive cells
within the endosteal and lineage-committed cells in the central
marrow regions. Herein, we now demonstrate that these 2 subpopulations
exhibit a striking difference in the expression of a cell surface
adhesion molecule, with populations enriched for murine and human
hemopoietic stem cells expressing the carbohydrate hyaluronic acid
(HA). Furthermore, the presence of this glycosaminoglycan appears
critical for the spatial distribution of transplanted stem cells in
vivo. In addition, we also demonstrate that the binding of HA by a
surrogate ligand results in marked inhibition of primitive hemopoietic
cell proliferation and granulocyte differentiation. Collectively, these
data describe an important yet previously unrecognized role for
HA in the biology of primitive hemopoietic progenitor cells.
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