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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3189-3202
Role of Members of the Wnt Gene Family in Human Hematopoiesis
David J. Van Den Berg,
Arun K. Sharma,
Edward Bruno, and
Ron Hoffman
From the Center for Molecular Hematopoiesis and the Section of
Hematology/Oncology, the Department of Medicine, University of Illinois
at Chicago.
The hematopoietic system is derived from ventral mesoderm. A number
of genes that are important in mesoderm development have been
identified including members of the transforming growth factor- (TGF-) superfamily, the fibroblast growth factor (FGF) family, and
the Wnt gene family. Because TGF- plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of the Wnt gene family, may play a role in hematopoiesis. Three
members of the Wnt gene family (Wnt-5A, Wnt-2B,
and Wnt-10B) were identified and cloned from human fetal bone
stromal cells. These genes are expressed to varying levels in
hematopoietic cell lines derived from T cells, B cells, myeloid cells,
and erythroid cells; however, only Wnt-5A was expressed in
CD34+Lin primitive progenitor cells. The
in vitro biological activity of these Wnt genes on
CD34+Lin hematopoietic progenitors was
determined in a feeder cell coculture system and assayed by
quantitating progenitor cell numbers, CD34+ cell numbers,
and numbers of differentiated cell types. The number of hematopoietic
progenitor cells was markedly affected by exposure to stromal cell
layers expressing Wnt genes with 10- to 20-fold higher numbers
of mixed colony-forming units (CFU-MIX), 1.5- to 2.6-fold higher
numbers of CFU-granulocyte macrophage (CFU-GM), and greater than
10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared
with the controls. Colony formation by cells expanded on the
Wnt-expressing cocultures was similar for each of the three
genes, indicating similar action on primitive progenitor cells;
however, Wnt-10B showed differential activity on erythroid
progenitors (BFU-E) compared with Wnt-5A and Wnt-2B.
Cocultures containing Wnt-10B alone or in combination with all
three Wnt genes had threefold to fourfold lower BFU-E colony
numbers than the Wnt-5A- or Wnt-2B-expressing
cocultures. The frequency of CD34+ cells was higher in
Wnt-expressing cocultures and cellular morphology indicated
that coculture in the presence of Wnt genes resulted in higher
numbers of less differentiated hematopoietic cells and fewer mature
cells than controls. These data indicate that the gene products of the
Wnt family function as hematopoietic growth factors, and that
they may exhibit higher specificity for earlier progenitor cells.
© 1998 by The American Society of Hematology.
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