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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2696-2703. Prepublished online as a Blood First Edition Paper on July 13, 2007; DOI 10.1182/blood-2007-03-082206. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-03-082206v1 110/7/2696    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 De Smedt, M. Articles by Plum, J. Search for Related Content PubMed PubMed Citation Articles by De Smedt, M. Articles by Plum, J. Related Collections Immunobiology Signal Transduction Gene Expression Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY Notch signaling induces cytoplasmic CD3 expression in human differentiating NK cells Magda De Smedt1, Tom Taghon1, Inge Van de Walle1, Greet De Smet1, Georges Leclercq1, and Jean Plum1 1 Department of Clinical Chemistry, Microbiology, and Immunology, Ghent University Hospital, Ghent, Belgium It has been proposed that heterogeneity in natural killer (NK)–cell phenotype and function can be achieved through distinct thymic and bone marrow pathways of NK-cell development. Here, we show a link between Notch signaling and the generation of intracellular CD3 (cyCD3)–expressing NK cells, a cell population that can be detected in vivo. Differentiation of human CD34+ cord blood progenitors in IL-15–supplemented fetal thymus organ culture or OP9-Delta-like 1 (DL1) coculture resulted in a high percentage of cyCD3+ NK cells that was blocked by the -secretase inhibitor DAPT. The requirement for Notch signaling to generate cyCD3+ NK cells was further illustrated by transduction of CD34+ cord blood (CB) cells with either the active intracellular part of Notch or the dominant-negative mutant of mastermind-like protein 1 that resulted in the generation of NK cells with respectively high or low frequencies of cyCD3. Human thymic CD34+ progenitor cells displayed the potential to generate cyCD3+ NK cells, even in the absence of Notch/DL1 signaling. Peripheral blood NK cells were unable to induce cyCD3 expression after DL1 exposure, indicating that Notch-dependent cyCD3 expression can only be achieved during the early phase of NK-cell differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Van Coppernolle, G. Verstichel, F. Timmermans, I. Velghe, D. Vermijlen, M. De Smedt, G. Leclercq, J. Plum, T. Taghon, B. Vandekerckhove, et al. Functionally Mature CD4 and CD8 TCR{alpha}{beta} Cells Are Generated in OP9-DL1 Cultures from Human CD34+ Hematopoietic Cells J. Immunol., October 15, 2009; 183(8): 4859 - 4870. [Abstract] [Full Text] [PDF] F. Timmermans, I. Velghe, L. Vanwalleghem, M. De Smedt, S. Van Coppernolle, T. Taghon, H. D. Moore, G. Leclercq, A. W. Langerak, T. Kerre, et al. Generation of T Cells from Human Embryonic Stem Cell-Derived Hematopoietic Zones J. Immunol., June 1, 2009; 182(11): 6879 - 6888. [Abstract] [Full Text] [PDF] K. Haraguchi, T. Suzuki, N. Koyama, K. Kumano, F. Nakahara, A. Matsumoto, Y. Yokoyama, M. Sakata-Yanagimoto, S. Masuda, T. Takahashi, et al. Notch Activation Induces the Generation of Functional NK Cells from Human Cord Blood CD34-Positive Cells Devoid of IL-15 J. Immunol., May 15, 2009; 182(10): 6168 - 6178. [Abstract] [Full Text] [PDF] O. H. Cho, H. M. Shin, L. Miele, T. E. Golde, A. Fauq, L. M. Minter, and B. A. Osborne Notch Regulates Cytolytic Effector Function in CD8+ T Cells J. Immunol., March 15, 2009; 182(6): 3380 - 3389. [Abstract] [Full Text] [PDF]

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