Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation.
Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct Notch ligands. Using a cell coculture assay we observed that the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell population coexpressing CD4 and CD8. Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis.
Jaleco
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Instituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal.
Neves
H
H
Hooijberg
E
E
Gameiro
P
P
Clode
N
N
Haury
M
M
Henrique
D
D
Parreira
L
L
D018952:Antigens, CD34; D016175:B-Lymphocyte Subsets / Q000166:cytology; D001402:B-Lymphocytes / Q000166:cytology; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins; D019409:Interleukin-15 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D007694:Killer Cells, Natural; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology*; D008221:Lymphoid Tissue / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D051941:fms-Like Tyrosine Kinase 3
D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D019409:Interleukin-15; D015851:Interleukin-7; D047908:Intracellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C064045:delta protein; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3