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Molecular and Cellular Biology, September 1998, p. 5247-5255, Vol. 18, No. 9
Division of Cellular and Gene
Therapy1 and
Division of Monoclonal
Antibodies,2 Office of Therapeutics Research
and Review, Center for Biologics Evaluation and Research, Rockville,
Maryland 20852
Received 9 December 1997/Returned for modification 27 January
1998/Accepted 22 June 1998
A close relationship exists between adipocyte differentiation of
stromal cells and their capacity to support hematopoiesis. The
molecular basis for this is unknown. We have studied whether dlk, an
epidermal growth factor-like molecule that intervenes in adipogenesis
and fetal liver hematopoiesis, affects both stromal cell adipogenesis
and B-cell lymphopoiesis in an established pre-B-cell culture system.
Pre-B-cell cultures require both soluble interleukin-7 (IL-7) and
interactions with stromal cells to promote cell growth and prevent
B-cell maturation or apoptosis. We found that BALB/c 3T3 fibroblasts
express dlk and function as stromal cells. Transfection of these cells
with antisense dlk decreased dlk expression and increased
insulin-induced adipocytic differentiation. When antisense transfectants were used as stroma, IL-7 was no longer required to
support the growth of pre-B cells and prevent maturation or apoptosis.
Antisense dlk transfectants of S10 stromal cells also promoted
pre-B-cell growth in the absence of IL-7. These results show that
modulation of dlk on stromal cells can influence their adipogenesis and
the IL-7 requirements of the pre-B cells growing in contact with them.
These results indicate that dlk influences differentiation signals
directed both to the stromal cells and to the lymphocyte precursors,
suggesting that dlk may play an important role in the bone marrow
hematopoietic environment.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Modulated Expression of the Epidermal Growth
Factor-Like Homeotic Protein dlk Influences Stromal-Cell-Pre-B-Cell
Interactions, Stromal Cell Adipogenesis, and Pre-B-Cell
Interleukin-7 Requirements
*
Corresponding author. Mailing address: Division of
Monoclonal Antibodies, Office of Therapeutics Research and Review,
Center for Biologics Evaluation and Research, 1401 Rockville Pike,
Rockville, MD 20852. Phone: (301) 827-0709. Fax: (301) 827-0852. E-mail: laborda{at}helix.nih.gov.
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