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Hematopoietic defects in mice lacking the sialomucin CD34
J Cheng, S Baumhueter, G Cacalano, K Carver-Moore, H Thibodeaux, R Thomas, HE Broxmeyer, S Cooper, N Hague, M Moore and LA Lasky
Department of Molecular Oncology, Genentech, Inc, South San Francisco, CA,
94108, USA.
Although the pluripotent hematopoietic stem cell can only be definitively
identified by its ability to reconstitute the various mature blood
lineages, a diversity of cell surface antigens have also been specifically
recognized on this subset of hematopoietic progenitors. One such stem
cell-associated antigen is the sialomucin CD34, a highly O-glycosylated
cell surface glycoprotein that has also been shown to be expressed on all
vascular endothelial cells throughout murine embryogenesis as well as in
the adult. The functional significance of CD34 expression on hematopoietic
progenitor cells and developing blood vessels is unknown. To analyze the
involvement of CD34 in hematopoiesis, we have produced both embryonic stem
(ES) cells and mice that are null for the expression of this mucin.
Analysis of yolk saclike hematopoietic development in embryoid bodies
derived from CD34- null ES cells showed a significant delay in both
erythroid and myeloid differentiation that could be reversed by
transfection of the mutant ES cells with CD34 constructs expressing either
a complete or truncated cytoplasmic domain. Measurements of colony-forming
activity of hematopoietic progenitor cells derived from yolk sacs or fetal
livers isolated from CD34-null embryos also showed a decreased number of
these precursor cells. In spite of these diminished embryonic hematopoietic
progenitor numbers, the CD34-null mice developed normally, and the
hematopoietic profile of adult blood appeared typical. However, the
colony-forming activity of hematopoietic progenitors derived from both bone
marrow and spleen is significantly reduced in adult CD34-deficient animals,
and these CD34-deficient progenitors also appear to be unable to expand in
liquid cultures in response to hematopoietic growth factors. Even with
these apparent progenitor cell deficiencies, CD34- null animals showed
kinetics of erythroid, myeloid, and platelet recovery after sublethal
irradiation that are indistinguishable from wild-type mice. These data
strongly suggest that CD34 plays an important role in the formation of
progenitor cells during both embryonic and adult hematopoiesis. However,
the hematopoietic sites of adult CD34-deficient mice may still have a
significant reservoir of progenitor cells that allows for normal recovery
after nonmyeloablative peripheral cell depletion.
Volume 87,
Issue 2,
pp. 479-490,
01/15/1996
Copyright © 1996 by The American Society of Hematology

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