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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 950-957
Mouse Jagged2 is differentially expressed in
hematopoietic progenitors and endothelial cells and promotes the
survival and proliferation of hematopoietic progenitors by direct
cell-to-cell contact
Schickwann Tsai,
Jutta Fero, and
Steve Bartelmez
From the Department of Medicine, Mount Sinai School of
Medicine, New York, NY; the Department of Pathology, University of
Washington, and the Seattle Biomedical Research Institute, Seattle, WA.
To study the regulation of the early stages of hematopoiesis, cDNA
representational difference analysis was used to isolate genes that
were differentially expressed in primitive hematopoietic progenitors.
The reasoning was that such genes were more likely to provide functions
important to hematopoietic stem cells and progenitors. One of the genes
identified through this approach encodes mouse Jagged2
(mJagged2). Using quantitative reverse
transcription-polymerase chain reaction, it was shown that
mJagged2 was differentially expressed in
c-kit+ hematopoietic progenitors, including those with
the phenotypes of Lin c-kit+
Rhlo Holo and Lin
c-kit+ Rhhi Holo, and that they
have been shown to be highly enriched for long-term and short-term
repopulating hematopoietic stem cells, respectively. Western blot
analyses showed that endothelial cells also expressed high levels of
Jagged2, but stromal fibroblasts did not. Using a
coculture system we found that exogenous, full-length mJagged2 promoted
the survival and proliferation of hematopoietic progenitors, including
the high-proliferative potential colony-forming cells. Direct
cell-to-cell contact was required for this effect. Taken together,
these findings indicate that both c-kit+ hematopoietic
progenitors and endothelial cells express Jagged2 and that exogenous,
full-length Jagged2 promotes the survival and proliferation of
hematopoietic progenitors.
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