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

Notch signaling is known to differentially affect the development of lympho id B and T cell lineages, but it remains unclear whether such effects are s pecifically dependent on distinct Notch ligands. Using a cell coculture ass ay we observed that the Notch ligand Delta-1 completely inhibits the differ entiation 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/N K 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 Jag ged-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 furt her address cell-fate decision processes in lymphopoiesis.