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Original Article

^a Instituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
^b Vrije Universiteit Medical Center, Department of Pathology (PA 312), de Boelelaan 1117, NL-1081 HV Amsterdam
^c Serviço de Hematologia, Instituto Português de Oncologia, 1099-023 Lisboa, Portugal
^d Serviço de Obstetrícia e Ginecologia, Hospital de Santa Maria, 1649-028 Lisboa, Portugal
^e Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal
Instituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa Av., Prof. Egas Moniz, 1649-028, Lisboa, Portugal.351-21-794-0058351-21-794-1364

hleonor{at}fm.ul.pt

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.

Key Words: cell-fate decision genes • lymphopoiesis • S17 cells • Notch signaling • B and T cells

A.C. Jaleco and H. Neves contributed equally to this work.

© 2001 The Rockefeller University Press

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