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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2002-10-3261. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3261v1 102/7/2444    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 García-Peydró, M. Articles by Toribio, M. L. Search for Related Content PubMed PubMed Citation Articles by García-Peydró, M. Articles by Toribio, M. L. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 October 2003, Vol. 102, No. 7, pp. 2444-2451 HEMATOPOIESIS Sustained Notch1 signaling instructs the earliest human intrathymic precursors to adopt a T-cell fate in fetal thymus organ culture Marina García-Peydró, Virginia G. de Yébenes, and María L. Toribio From the Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autónoma de Madrid, Madrid, Spain. Notch1 activity is essential for the specification of T-lineage fate in hematopoietic progenitors. Once the T-cell lineage is specified, T-cell precursors in the thymus must choose between and lineages. However, the impact of Notch1 signaling on intrathymic pro-T cells has not been addressed directly. To approach this issue, we used retroviral vectors to express constitutively active Notch1 in human thymocyte progenitors positioned at successive developmental stages, and we followed their differentiation in fetal thymus organ culture (FTOC). Here we show that sustained Notch1 signaling impairs progression to the double-positive (DP) stage and efficiently diverts the earliest thymic progenitors from the main T-cell pathway toward development of T cells. The impact of Notch1 signaling on skewed production decreases progressively along intrathymic maturation and is restricted to precursor stages upstream of the pre-T-cell receptor checkpoint. Close to and beyond that point, Notch1 is not further able to instruct cell fate, but promotes an abnormal expansion of -committed thymocytes. These results stress the stage-specific impact of Notch1 signaling in intrathymic differentiation and suggest that regulation of Notch1 activity at defined developmental windows is essential to control versus T-cell development and to avoid deregulated expansion of -lineage cells. (Blood. 2003;102:2444-2451) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. N. Navarro, G. Nusspaumer, P. Fuentes, S. Gonzalez-Garcia, J. Alcain, and M. L. Toribio Identification of CMS as a cytosolic adaptor of the human pT{alpha} chain involved in pre-TCR function Blood, December 15, 2007; 110(13): 4331 - 4340. [Abstract] [Full Text] [PDF] M. De Smedt, T. Taghon, I. Van de Walle, G. De Smet, G. Leclercq, and J. Plum Notch signaling induces cytoplasmic CD3{epsilon} expression in human differentiating NK cells Blood, October 1, 2007; 110(7): 2696 - 2703. [Abstract] [Full Text] [PDF] M. Garcia-Peydro, V. 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