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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1505-1511
RAPID COMMUNICATION
Stromal Expression of Jagged 1 Promotes Colony Formation by Fetal
Hematopoietic Progenitor Cells
Philip Jones,
Gill May,
Lyn Healy,
John Brown,
Gerald Hoyne,
Sylvie Delassus, and
Tariq Enver
From the Section of Gene Function and Regulation & Leukaemia Research
Fund Centre, Chester Beatty Laboratories, Institute of Cancer Research,
London; and the Department of Respiratory Medicine, University of
Edinburgh, Edinburgh, UK.
The Notch signaling system regulates proliferation and
differentiation in many tissues. Notch is a transmembrane receptor activated by ligands expressed on adjacent cells. Hematopoietic stem
cells and early progenitors express Notch, making the stromal cells
which form cell-cell contacts with progenitor cells candidate ligand-presenting cells in the hematopoietic microenvironment. Therefore, we examined primary stromal cell cultures for expression of
Notch ligands. Using reverse transcription-polymerase chain reaction,
in situ hybridization, immunohistochemistry, and Western blotting, we
demonstrate expression of Jagged 1 in primary stromal cultures. To
investigate if the stromal expression of Jagged 1 has functional
effects on hematopoietic progenitors, we cultured CD34+,
c-kit+ hematopoietic progenitor cells derived
from the aorto gonadal mesonephros region of day 11 mouse embryos on
the Jagged 1 stromal cell line S17 and on S17 cells
engineered to express Jagged 1. The presence of Jagged 1 increased the
number of colonies formed in subsequent methylcellulose culture
fourfold. Larger increases in colony numbers were observed under the
same culture conditions with CD34+,
c-kit+ hematopoietic progenitor cells derived
from d11 fetal liver. These results obtained in vitro table Jagged 1 as
a candidate regulator of stem cell fate in the context of stromal
microenvironments in vivo.
© 1998 by The American Society of Hematology.
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