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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1 October 2001
Article|
October 01 2001
Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation
Ana C. Jaleco,
Ana C. Jaleco
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
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Hélia Neves,
Hélia Neves
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
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Erik Hooijberg,
Erik Hooijberg
bVrije Universiteit Medical Center, Department of Pathology (PA 312), de Boelelaan 1117, NL-1081 HV Amsterdam
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Paula Gameiro,
Paula Gameiro
cServiço de Hematologia, Instituto Português de Oncologia, 1099-023 Lisboa, Portugal
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Nuno Clode,
Nuno Clode
dServiço de Obstetrícia e Ginecologia, Hospital de Santa Maria, 1649-028 Lisboa, Portugal
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Matthias Haury,
Matthias Haury
eInstituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal
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Domingos Henrique,
Domingos Henrique
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
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Leonor Parreira
Leonor Parreira
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
eInstituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal
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Ana C. Jaleco
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
Hélia Neves
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
Erik Hooijberg
bVrije Universiteit Medical Center, Department of Pathology (PA 312), de Boelelaan 1117, NL-1081 HV Amsterdam
Paula Gameiro
cServiço de Hematologia, Instituto Português de Oncologia, 1099-023 Lisboa, Portugal
Nuno Clode
dServiço de Obstetrícia e Ginecologia, Hospital de Santa Maria, 1649-028 Lisboa, Portugal
Matthias Haury
eInstituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal
Domingos Henrique
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
Leonor Parreira
aInstituto de Histologia e Embriologia, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal
eInstituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal
Abbreviations used in this paper: CB, cord blood; eGFP, enhanced green fluorescent protein; NK, natural killer.
A.C. Jaleco and H. Neves contributed equally to this work.
Received:
May 18 2001
Revision Requested:
August 20 2001
Accepted:
August 27 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 194 (7): 991–1002.
Article history
Received:
May 18 2001
Revision Requested:
August 20 2001
Accepted:
August 27 2001
Citation
Ana C. Jaleco, Hélia Neves, Erik Hooijberg, Paula Gameiro, Nuno Clode, Matthias Haury, Domingos Henrique, Leonor Parreira; Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation. J Exp Med 1 October 2001; 194 (7): 991–1002. doi: https://doi.org/10.1084/jem.194.7.991
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