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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2446-2452. Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-05-2090. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-05-2090v1 107/6/2446    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dontje, W. Articles by Blom, B. Search for Related Content PubMed PubMed Citation Articles by Dontje, W. Articles by Blom, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 25, 2005 Accepted November 8, 2005 DeltaLike1 induced Notch1 signalling regulates the human plasmacytoid dendritic cell versus T cell lineage decision through control of GATA-3 and Spi-B Wendy Dontje, Remko Schotte, Tom Cupedo, Maho Nagasawa, Ferenc Scheeren, Ramon Gimeno, Hergen Spits, and Bianca Blom* Department of Cell Biology & Histology, Academic Medical Center (AMC) at the University of Amsterdam, Amsterdam, The Netherlands * Corresponding author; email: b.blom{at}amc.uva.nl. Human early thymic precursors have the potential to differentiate into multiple cell lineages, including T cells and plasmacytoid dendritic cells (pDC). This decision is guided by the induction or silencing of lineage specific transcription factors. The ETS-family member Spi-B is a key regulator of pDC development, while T cell development is critically dependent on GATA-3. Here we show that triggering of the Notch1 signaling pathway by DeltaLike1 controls the T/pDC lineage decision by regulating the balance between these factors. CD34+CD1a- thymic progenitor cells express Notch1, but downregulate this receptor when differentiating into pDC. Upon co-culture with stromal cell lines expressing either human DeltaLike1 (DL1) or Jagged1 (Jag1) Notch ligands, thymic precursors express GATA-3 and develop into CD4+CD8+TCR+ T cells. On the other hand, DL1, but not Jag1 downregulates Spi-B expression, resulting in impaired development of pDC. The Notch1 induced block in pDC development can be relieved through the ectopic expression of Spi-B. These data indicate that DL1-induced activation of the Notch1 pathway controls the lineage commitment of early thymic precursors by altering the levels between Spi-B and GATA-3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. van Tetering, P. van Diest, I. Verlaan, E. van der Wall, R. Kopan, and M. Vooijs Metalloprotease ADAM10 Is Required for Notch1 Site 2 Cleavage J. Biol. Chem., November 6, 2009; 284(45): 31018 - 31027. [Abstract] [Full Text] [PDF] S.-O. Yoon, X. Zhang, P. Berner, B. Blom, and Y. S. Choi Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis J. Immunol., July 1, 2009; 183(1): 352 - 358. [Abstract] [Full Text] [PDF] Y.-C. Wang, X.-B. Hu, F. He, F. Feng, L. Wang, W. Li, P. Zhang, D. Li, Z.-S. Jia, Y.-M. Liang, et al. Lipopolysaccharide-induced Maturation of Bone Marrow-derived Dendritic Cells Is Regulated by Notch Signaling through the Up-regulation of CXCR4 J. Biol. Chem., June 5, 2009; 284(23): 15993 - 16003. [Abstract] [Full Text] [PDF] H. Schmidlin, S. A. Diehl, M. Nagasawa, F. A. Scheeren, R. Schotte, C. H. Uittenbogaart, H. Spits, and B. 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