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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4132-4141
HEMATOPOIESIS
WNT signaling modulates the diversification of
hematopoietic cells
Carlene Brandon,
Leonard M. Eisenberg, and
Carol A. Eisenberg
From the Department of Cell Biology and Anatomy,
Medical University of South Carolina, Charleston, SC.
WNT proteins compose a family of secreted signaling molecules that
regulate cell fate and behavior. The possible influence of WNTs on
hematopoietic cell fate was examined. Both hematopoietic progenitor cell (HPC)-enriched embryonic avian bone marrow cells and
the quail mesodermal stem cell line QCE6 were used for these studies.
Under optimized conditions, the bone marrow and QCE6 cells behaved
identically and developed into red blood cells (RBCs), monocytes,
macrophages, granulocytes, and thrombocytes. This broad range of blood
cell phenotypes exhibited by QCE6 cells was dependent on their active
expression of WNT11. However, when QCE6 cells were prevented from
producing WNT11 by expression of a stably transfected WNT11 antisense
transgenethe cultures were dominated by highly vacuolated
macrophages. RBCs were absent from these cultures, and the presence of
monocytes was greatly diminished. Exposure of these WNT11 antisense
cells to soluble WNT11 or WNT5a restored the broad range of blood cell
phenotypes exhibited by parental QCE6 cells. Overexpression of WNT
protein in QCE6 cells further increased the prevalence of RBCs and
monocytes and greatly diminished the appearance of macrophages.
Accordingly, treatment of HPC-enriched bone marrow cultures with
soluble WNT11 or WNT5a inhibited macrophage formation. Instead,
monocytes and RBCs were the prevalent cells displayed by WNT-treated
bone marrow cultures. Together, these data indicate that WNTs may play
a major role in regulating hematopoietic cell fate.
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