The Notch/Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro.
The cell surface receptor Notch1 is expressed on CD34+ hematopoietic precursors, whereas one of its ligands, Jagged1, is expressed on bone marrow stromal 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 the absence of recombinant growth factors, Jagged1 decreased myeloid colony formation by CD34+ cells, as well as 3H-thymidine incorporation and entry into S phase. In the presence of a strong cytokine signal to proliferate and mature, (interleukin 3 [IL-3] and IL-6, stem cell factor [SCF], and G-CSF), Jagged1 did not significantly alter either the fold expansion or the types of colonies formed by CD34+ cells. However, in the presence of SCF alone, Jagged1 increased erythroid colony formation twofold. These results demonstrate that Notch can modulate a growth factor signal, and that in the absence of growth factor stimulation, the Jagged1-Notch pathway preserves CD34+ cells in an immature state.
Walker
L
L
Department of Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-1781, USA.
Lynch
M
M
Silverman
S
S
Fraser
J
J
Boulter
J
J
Weinmaster
G
G
Gasson
J C
JC
D016475:3T3 Cells; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002135:Calcium-Binding Proteins; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D011506:Proteins / Q000502:physiology*; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D019089:Stem Cell Factor / Q000502:physiology; D014162:Transfection
D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007377:Interleukin-3; D015850:Interleukin-6; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor