Hematopoietic defects in mice lacking the sialomucin CD34

J. Cheng, S. Baumhueter, G. Cacalano, K. Carver-Moore, H. Thibodeaux, R. Thomas, Hal Broxmeyer, S. Cooper, N. Hague, M. Moore, L. A. Lasky

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Abstract

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 stern 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 sac- like 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 end 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.

Original languageEnglish (US)
Pages (from-to)479-490
Number of pages12
JournalBlood
Volume87
Issue number2
StatePublished - Jan 15 1996
Externally publishedYes

Fingerprint

Sialomucins
Hematopoietic Stem Cells
Stem cells
Yolk Sac
Stem Cells
Hematopoiesis
Embryonic Stem Cells
Defects
Embryoid Bodies
Pluripotent Stem Cells
Animals
Blood
Membrane Glycoproteins
Mucins
Surface Antigens
Recovery
Embryonic Development
Transfection
Blood Vessels
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Cheng, J., Baumhueter, S., Cacalano, G., Carver-Moore, K., Thibodeaux, H., Thomas, R., ... Lasky, L. A. (1996). Hematopoietic defects in mice lacking the sialomucin CD34. Blood, 87(2), 479-490.

Hematopoietic defects in mice lacking the sialomucin CD34. / Cheng, J.; Baumhueter, S.; Cacalano, G.; Carver-Moore, K.; Thibodeaux, H.; Thomas, R.; Broxmeyer, Hal; Cooper, S.; Hague, N.; Moore, M.; Lasky, L. A.

In: Blood, Vol. 87, No. 2, 15.01.1996, p. 479-490.

Research output: Contribution to journalArticle

Cheng, J, Baumhueter, S, Cacalano, G, Carver-Moore, K, Thibodeaux, H, Thomas, R, Broxmeyer, H, Cooper, S, Hague, N, Moore, M & Lasky, LA 1996, 'Hematopoietic defects in mice lacking the sialomucin CD34', Blood, vol. 87, no. 2, pp. 479-490.
Cheng J, Baumhueter S, Cacalano G, Carver-Moore K, Thibodeaux H, Thomas R et al. Hematopoietic defects in mice lacking the sialomucin CD34. Blood. 1996 Jan 15;87(2):479-490.
Cheng, J. ; Baumhueter, S. ; Cacalano, G. ; Carver-Moore, K. ; Thibodeaux, H. ; Thomas, R. ; Broxmeyer, Hal ; Cooper, S. ; Hague, N. ; Moore, M. ; Lasky, L. A. / Hematopoietic defects in mice lacking the sialomucin CD34. In: Blood. 1996 ; Vol. 87, No. 2. pp. 479-490.
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abstract = "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 stern 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 sac- like 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 end 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.",
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