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Jagged2 acts as a Delta-like Notch ligand during early hematopoietic cell fate decisions

Inge Van de Walle, Greet De Smet UGent, Martina Gärtner, Magda De Smedt, Els Waegemans, Bart Vandekerckhove UGent, Georges Leclercq UGent, Jean Plum, Jon C Aster, Irwin D Bernstein, et al. (2011) BLOOD. 117(17). p.4449-4459
abstract
Notch signaling critically mediates various hematopoietic lineage decisions and is induced in mammals by Notch ligands that are classified into 2 families, Delta-like (Delta-like-1, -3 and -4) and Jagged (Jagged1 and Jagged2), based on structural homology with both Drosophila ligands Delta and Serrate, respectively. Because the functional differences between mammalian Notch ligands were still unclear, we have investigated their influence on early human hematopoiesis and show that Jagged2 affects hematopoietic lineage decisions very similarly as Delta-like-1 and -4, but very different from Jagged1. OP9 coculture experiments revealed that Jagged2, like Delta-like ligands, induces T-lineage differentiation and inhibits B-cell and myeloid development. However, dose-dependent Notch activation studies, gene expression analysis, and promoter activation assays indicated that Jagged2 is a weaker Notch1-activator compared with the Delta-like ligands, revealing a Notch1 specific signal strength hierarchy for mammalian Notch ligands. Strikingly, Lunatic-Fringe-mediated glycosylation of Notch1 potentiated Notch signaling through Delta-like ligands and also Jagged2, in contrast to Jagged1. Thus, our results reveal a unique role for Jagged1 in preventing the induction of T-lineage differentiation in hematopoietic stem cells and show an unexpected functional similarity between Jagged2 and the Delta-like ligands.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
B-CELL, EPITHELIAL-CELLS, STEM-CELLS, T-CELLS, TCR-ALPHA-BETA, IN-VITRO, IMMUNE-SYSTEM, PROGENITOR CELLS, DIFFERENTIATION, EXPRESSION
journal title
BLOOD
Blood
volume
117
issue
17
pages
4449 - 4459
Web of Science type
Article
Web of Science id
000289984800010
JCR category
HEMATOLOGY
JCR impact factor
9.898 (2011)
JCR rank
2/68 (2011)
JCR quartile
1 (2011)
ISSN
0006-4971
DOI
10.1182/blood-2010-06-290049
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1235372
handle
http://hdl.handle.net/1854/LU-1235372
date created
2011-05-25 08:42:34
date last changed
2016-12-19 15:44:49
@article{1235372,
  abstract     = {Notch signaling critically mediates various hematopoietic lineage decisions and is induced in mammals by Notch ligands that are classified into 2 families, Delta-like (Delta-like-1, -3 and -4) and Jagged (Jagged1 and Jagged2), based on structural homology with both Drosophila ligands Delta and Serrate, respectively. Because the functional differences between mammalian Notch ligands were still unclear, we have investigated their influence on early human hematopoiesis and show that Jagged2 affects hematopoietic lineage decisions very similarly as Delta-like-1 and -4, but very different from Jagged1. OP9 coculture experiments revealed that Jagged2, like Delta-like ligands, induces T-lineage differentiation and inhibits B-cell and myeloid development. However, dose-dependent Notch activation studies, gene expression analysis, and promoter activation assays indicated that Jagged2 is a weaker Notch1-activator compared with the Delta-like ligands, revealing a Notch1 specific signal strength hierarchy for mammalian Notch ligands. Strikingly, Lunatic-Fringe-mediated glycosylation of Notch1 potentiated Notch signaling through Delta-like ligands and also Jagged2, in contrast to Jagged1. Thus, our results reveal a unique role for Jagged1 in preventing the induction of T-lineage differentiation in hematopoietic stem cells and show an unexpected functional similarity between Jagged2 and the Delta-like ligands.},
  author       = {Van de Walle, Inge and De Smet, Greet and G{\"a}rtner, Martina and De Smedt, Magda and Waegemans, Els and Vandekerckhove, Bart and Leclercq, Georges and Plum, Jean and Aster, Jon C and Bernstein, Irwin D and Guidos, Cynthia J and Kyewski, Bruno and Taghon, Tom},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keyword      = {B-CELL,EPITHELIAL-CELLS,STEM-CELLS,T-CELLS,TCR-ALPHA-BETA,IN-VITRO,IMMUNE-SYSTEM,PROGENITOR CELLS,DIFFERENTIATION,EXPRESSION},
  language     = {eng},
  number       = {17},
  pages        = {4449--4459},
  title        = {Jagged2 acts as a Delta-like Notch ligand during early hematopoietic cell fate decisions},
  url          = {http://dx.doi.org/10.1182/blood-2010-06-290049},
  volume       = {117},
  year         = {2011},
}

Chicago
Van de Walle, Inge, Greet De Smet, Martina Gärtner, Magda De Smedt, Els Waegemans, Bart Vandekerckhove, Georges Leclercq, et al. 2011. “Jagged2 Acts as a Delta-like Notch Ligand During Early Hematopoietic Cell Fate Decisions.” Blood 117 (17): 4449–4459.
APA
Van de Walle, I., De Smet, G., Gärtner, M., De Smedt, M., Waegemans, E., Vandekerckhove, B., Leclercq, G., et al. (2011). Jagged2 acts as a Delta-like Notch ligand during early hematopoietic cell fate decisions. BLOOD, 117(17), 4449–4459.
Vancouver
1.
Van de Walle I, De Smet G, Gärtner M, De Smedt M, Waegemans E, Vandekerckhove B, et al. Jagged2 acts as a Delta-like Notch ligand during early hematopoietic cell fate decisions. BLOOD. 2011;117(17):4449–59.
MLA
Van de Walle, Inge, Greet De Smet, Martina Gärtner, et al. “Jagged2 Acts as a Delta-like Notch Ligand During Early Hematopoietic Cell Fate Decisions.” BLOOD 117.17 (2011): 4449–4459. Print.