Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation

Author:

Jaleco Ana C.1,Neves Hélia1,Hooijberg Erik2,Gameiro Paula3,Clode Nuno4,Haury Matthias5,Henrique Domingos1,Parreira Leonor15

Affiliation:

1. Instituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal

2. Vrije Universiteit Medical Center, Department of Pathology (PA 312), de Boelelaan 1117, NL-1081 HV Amsterdam

3. Serviço de Hematologia, Instituto Português de Oncologia, 1099-023 Lisboa, Portugal

4. Serviço de Obstetrícia e Ginecologia, Hospital de Santa Maria, 1649-028 Lisboa, Portugal

5. Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal

Abstract

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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