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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1431-1439. Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-04-1293. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-04-1293v1 105/4/1431    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 La Motte-Mohs, R. N. Articles by Zúñiga-Pflücker, J. C. Search for Related Content PubMed PubMed Citation Articles by La Motte-Mohs, R. N. Articles by Zúñiga-Pflücker, J. C. Related Collections Hematopoiesis and Stem Cells Immunobiology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro Ross N. La Motte-Mohs, Elaine Herer, and Juan Carlos Zúñiga-Pflücker From the Department of Immunology, University of Toronto, Sunnybrook and Women's College Health Sciences Centre; Women's College Ambulatory Care Centre, The Women's College Campus of Sunnybrook and Women's Health Sciences Centre, Toronto, Ontario, Canada. The Notch signaling pathway plays a key role at several stages of T-lymphocyte differentiation. However, it remained unclear whether signals induced by the Notch ligand Delta-like 1 could support full T-cell differentiation from a defined source of human hematopoietic stem cells (HSCs) in vitro. Here, we show that human cord blood–derived HSCs cultured on Delta-like 1–expressing OP9 stromal cells undergo efficient T-cell lineage commitment and sustained T-cell differentiation. A normal stage-specific program of T-cell development was observed, including the generation of CD4 and CD8 –T-cell receptor (TCR)–bearing cells. Induction of T-cell differentiation was dependent on the expression of Delta-like 1 by the OP9 cells. Stimulation of the in vitro–differentiated T cells by TCR engagement induced the expression of T-cell activation markers and costimulatory receptors. These results establish an efficient in vitro coculture system for the generation of T cells from human HSCs, providing a new avenue for the study of early T-cell differentiation and function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Cooking up T cells Warren S. Pear Blood 2005 105: 1373-1374. [Full Text] [PDF] This article has been cited by other articles: 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] 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] S. Gonzalez-Garcia, M. Garcia-Peydro, E. Martin-Gayo, E. Ballestar, M. Esteller, R. Bornstein, J. L. de la Pompa, A. A. Ferrando, and M. L. Toribio CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia J. Exp. Med., April 13, 2009; 206(4): 779 - 791. [Abstract] [Full Text] [PDF] J. F. Hutton, T. Gargett, T. J. Sadlon, S. Bresatz, C. Y. Brown, H. Zola, M. F. Shannon, R. J. D'Andrea, and S. C. Barry Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells J. Leukoc. Biol., March 1, 2009; 85(3): 445 - 451. [Abstract] [Full Text] [PDF] F. Armstrong, P. B. de la Grange, B. Gerby, M.-C. Rouyez, J. Calvo, M. Fontenay, N. Boissel, H. Dombret, A. Baruchel, J. Landman-Parker, et al. NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity Blood, February 19, 2009; 113(8): 1730 - 1740. [Abstract] [Full Text] [PDF] R. Holmes and J. C. Zuniga-Pflucker The OP9-DL1 System: Generation of T-Lymphocytes from Embryonic or Hematopoietic Stem Cells In Vitro CSH Protocols, February 1, 2009; 2009(2): pdb.prot5156 - pdb.prot5156. [Abstract] [Full Text] E. M. Six, D. Bonhomme, M. Monteiro, K. Beldjord, M. Jurkowska, C. Cordier-Garcia, A. Garrigue, L. Dal Cortivo, B. Rocha, A. Fischer, et al. A human postnatal lymphoid progenitor capable of circulating and seeding the thymus J. Exp. Med., December 24, 2007; 204(13): 3085 - 3093. [Abstract] [Full Text] [PDF] Q. Wu, T. Kumagai, M. Kawahara, H. Ogawa, H. Hiura, Y. Obata, R. Takano, and T. Kono Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term. Reproduction, March 1, 2006; 131(3): 481 - 488. [Abstract] [Full Text] [PDF] M. De Smedt, I. Hoebeke, K. Reynvoet, G. Leclercq, and J. Plum Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment Blood, November 15, 2005; 106(10): 3498 - 3506. [Abstract] [Full Text] [PDF] C. Delaney, B. Varnum-Finney, K. Aoyama, C. Brashem-Stein, and I. D. 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