Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 2884-2897
Heparan Sulfate Proteoglycan Expression Is Induced During Early
Erythroid Differentiation of Multipotent Hematopoietic Stem Cells
Zofia Drzeniek,
Georg Stöcker,
Barbara Siebertz,
Ursula Just,
Timm Schroeder,
Wolfram Ostertag, and
Hans-Dieter Haubeck
From the Institute for Clinical Chemistry and Pathobiochemistry,
Medical Faculty, University of Technology, Aachen, Germany; Institute
for Clinical Molecular Biology-GSF Research Center, München,
Germany; and Heinrich-Pette-Institute for Experimental Virology and
Immunology, Hamburg, Germany.
Heparan sulfate (HS) proteoglycans of bone marrow (BM) stromal cells
and their extracellular matrix are important components of the
microenvironment of hematopoietic tissues and are involved in the
interaction of hematopoietic stem and stromal cells. Although previous
studies have emphasized the role of HS proteoglycan synthesis by BM
stromal cells, we have recently shown that the human hematopoietic progenitor cell line TF-1 also expressed an HS proteoglycan.
Immunochemical, reverse transcriptase-polymerase chain reaction
(RT-PCR), and Northern blot analysis of this HS proteoglycan showed
that it was not related to the syndecan family of HS proteoglycans or to glypican. To answer the question of whether the expression of HS
proteoglycans is associated with the differentiation state of
hematopoietic progenitor cells, we have analyzed the proteoglycan synthesis of several murine and human hematopoietic progenitor cell
lines. Proteoglycans were isolated from metabolically labeled cells and
purified by several chromatographic steps. Isolation and
characterization of proteoglycans from the cell lines HEL and ELM-D,
which like TF-1 cells have an immature erythroid phenotype, showed that
these cells synthesize the same HS proteoglycan, previously detected in
TF-1 cells, as a major proteoglycan. In contrast, cell lines of the
myeloid lineage, like the myeloblastic/promyelocytic cell lines B1 and
B2, do not express HS proteoglycans. Taken together, our data strongly
suggest that expression of this HS proteoglycan in hematopoietic
progenitor cell lines is associated with the erythroid lineage. To
prove this association we have analyzed the proteoglycan expression in
the nonleukemic multipotent stem cell line FDCP-Mix-A4 after induction
of erythroid or granulocytic differentiation. Our data show that HS
proteoglycan expression is induced during early erythroid
differentiation of multipotent hematopoietic stem cells. In contrast,
during granulocytic differentiation, no expression of HS proteoglycans
was observed.
