The Notch Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro

The cell surface receptor Notch1 is expressed on CD34(+) hematopoietic prec ursors, whereas one of its ligands, Jagged1, is expressed on bone marrow st romal cells. To examine the role of Notch signaling in early hematopoiesis, human CD34(+) cells were cultured in the presence or absence of exogenous cytokines on feeder layers that either did or did not express Jagged1. In t he absence of recombinant growth factors, Jagged1 decreased myeloid colony formation by CD34(+) cells, as wed as H-3-thymidine incorporation and entry into S phase. In the presence of a strong cytokine signal to proliferate a nd mature, (interleukin 3 [IL-3] and IL-6, stem cell factor [SCF], and G-CS F), Jagged1 did not significantly alter either the fold expansion or the ty pes of colonies formed by CD34(+) cells. However, in the presence of SCF al one, Jagged1 increased erythroid colony formation twofold. These results de monstrate that Notch can modulate a growth factor signal, and that in the a bsence of growth factor stimulation, the Jagged1-Notch pathway preserves CD 34(+) cells in an immature state.