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

doi:10.1084/jem.194.7.991

Published online 1 October 2001. doi:10.1084/jem.194.7.991

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© The Rockefeller University Press, 0022-1007/2001/10/991/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 7, October 1, 2001 991-1002

Original Article

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

Ana C. Jaleco^a, Hélia Neves^a, Erik Hooijberg^b, Paula Gameiro^c, Nuno Clode^d, Matthias Haury^e, Domingos Henrique^a, and Leonor Parreira^a,e
^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

Correspondence to: Leonor Parreira, Instituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa Av., Prof. Egas Moniz, 1649-028, Lisboa, Portugal. Tel:351-21-794-1364 Fax:351-21-794-0058 E-mail:hleonor{at}fm.ul.pt.

Notch signaling is known to differentially affect the developmentof lymphoid B and T cell lineages, but it remains unclear whethersuch effects are specifically dependent on distinct Notch ligands.Using a cell coculture assay we observed that the Notch ligandDelta-1 completely inhibits the differentiation of human hematopoieticprogenitors into the B cell lineage while promoting the emergenceof cells with a phenotype of T cell/natural killer (NK) precursors.In contrast, Jagged-1 did not disturb either B or T cell/NKdevelopment. Furthermore, cells cultured in the presence ofeither Delta-1 or Jagged-1 can acquire a phenotype of NK cells,and Delta-1, but not Jagged-1, permits the emergence of a denovo cell population coexpressing CD4 and CD8. Our results thusindicate that distinct Notch ligands can mediate differentialeffects of Notch signaling and provide a useful system to furtheraddress cell-fate decision processes in lymphopoiesis.

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

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