The Notch2-Jagged1 interaction mediates stem cell factor signaling in erythropoiesis.
Stem cell factor (SCF), the ligand for the c-kit receptor, is essential for the production of red blood cells during development and stress erythropoiesis. SCF promotes erythroblast proliferation and survival, while delaying erythroid differentiation through mechanisms that are largely unknown. In cultures of primary human differentiating erythroblasts, we found that SCF induces an increase in the expression of Notch2, a member of the Notch family implicated in the control of cell growth and differentiation. Functional inhibition of either Notch or its ligand Jagged1 inhibited the effects of SCF on erythroid cell expansion. SCF also induced the expression of Hes-1 and GATA-2, which may contribute to transduce Notch2 signals in response to SCF. Transduction of primary erythroid precursors with a dominant-negative Notch2 mutant inhibited both basal and SCF-mediated erythroblast expansion, and counteracted the effects of SCF on erythroblast differentiation. These findings provide a clue to understand the effects of increased proliferation and delayed differentiation elicited by SCF on the erythroid compartment and indicate Notch2 as a new player in the regulation of red cell differentiation.
Zeuner
A
A
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy. a.zeuner@iss.it
Francescangeli
F
F
Signore
M
M
Venneri
M A
MA
Pedini
F
F
Felli
N
N
Pagliuca
A
A
Conticello
C
C
De Maria
R
R
D018952:Antigens, CD34 / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism*; D000072056:Transcription Factor HES-1
D018952:Antigens, CD34; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D050989:GATA2 Transcription Factor; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051883:Receptor, Notch2; D000072099:Serrate-Jagged Proteins; D019089:Stem Cell Factor; D000072056:Transcription Factor HES-1; C000606273:JAG1 protein, human; C497764:NOTCH2 protein, human; C078493:HES1 protein, human