Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation

AC Jaleco, H Neves, E Hooijberg, P Gameiro… - The Journal of …, 2001 - rupress.org
AC Jaleco, H Neves, E Hooijberg, P Gameiro, N Clode, M Haury, D Henrique, L Parreira
The Journal of experimental medicine, 2001rupress.org
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 …
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.
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