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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3131-3137. Prepublished online as a Blood First Edition Paper on December 29, 2005; DOI 10.1182/blood-2005-08-3412. This Article Full Text (PDF) All Versions of this Article: 2005-08-3412v1 107/8/3131    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 Weerkamp, F. Articles by Staal, F. J Search for Related Content PubMed PubMed Citation Articles by Weerkamp, F. Articles by Staal, F. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 23, 2005 Accepted December 12, 2005 The human thymus contains multipotent progenitors with T/B-lymphoid, myeloid and erythroid lineage potential Floor Weerkamp, Miranda R Baert, Martijn H Brugman, Willem A Dik, Edwin F de Haas, Trudi P Visser, Christianne J de Groot, Gerard Wagemaker, Jacques J van Dongen, and Frank J Staal* Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands * Corresponding author; email: f.staal{at}erasmusmc.nl. It is a longstanding question which bone marrow-derived cell seeds the thymus and to what level this cell is committed to the T-cell lineage. We sought to elucidate this issue by examining gene expression, lineage potential and self-renewal capacity of the two most immature subsets in the human thymus, namely CD34+CD1a- and CD34+CD1a+ thymocytes. DNA microarrays revealed the presence of several myeloid and erythroid transcripts in CD34+CD1a-, but not in CD34+CD1a+ thymocytes. Lineage potential of both subpopulations was assessed using in vitro colony assays, bone marrow stroma cultures and in vivo transplantation into NOD/SCID mice. The CD34+CD1a- subset contained progenitors with lymphoid (both T and B), myeloid and erythroid lineage potential. Remarkably, development of CD34+CD1a- thymocytes towards the T-cell lineage, as shown by T-cell receptor delta gene rearrangements, could be reversed into a myeloid cell-fate. In contrast, the CD34+CD1a+ cells yielded only T cell progenitors, demonstrating their irreversible commitment to the T-cell lineage. Both CD34+CD1a- and CD34+CD1a+ thymocytes failed to repopulate NOD/SCID mice. We conclude that the human thymus is seeded by multipotent progenitors with a much broader lineage potential than previously assumed. These cells resemble hematopoietic stem cells, but, by analogy with murine thymocytes, apparently lack sufficient self-renewal capacity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. J.T. Staal and A. W. Langerak Signaling pathways involved in the development of T-cell acute lymphoblastic leukemia Haematologica, April 1, 2008; 93(4): 493 - 497. [Full Text] [PDF] S. Strehl, K. Nebral, M. Konig, J. Harbott, H. Strobl, R. Ratei, S. Struski, B. Bielorai, M. Lessard, M. Zimmermann, et al. ETV6-NCOA2: A Novel Fusion Gene in Acute Leukemia Associated with Coexpression of T-Lymphoid and Myeloid Markers and Frequent NOTCH1 Mutations Clin. Cancer Res., February 15, 2008; 14(4): 977 - 983. [Abstract] [Full Text] [PDF] Q.-L. Hao, A. A. George, J. Zhu, L. Barsky, E. Zielinska, X. Wang, M. Price, S. Ge, and G. M. Crooks Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors Blood, February 1, 2008; 111(3): 1318 - 1326. [Abstract] [Full Text] [PDF] 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] C. C. Tydell, E.-S. David-Fung, J. E. Moore, L. Rowen, T. Taghon, and E. V. Rothenberg Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte Developmental Pathway J. Immunol., July 1, 2007; 179(1): 421 - 438. [Abstract] [Full Text] [PDF] Z. Guo, M. Dose, D. Kovalovsky, R. Chang, J. O'Neil, A. T. Look, H. von Boehmer, K. Khazaie, and F. Gounari {beta}-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation Blood, June 15, 2007; 109(12): 5463 - 5472. [Abstract] [Full Text] [PDF] M. Cavazzana-Calvo, F. Carlier, F. Le Deist, E. Morillon, P. Taupin, D. Gautier, I. Radford-Weiss, S. Caillat-Zucman, B. Neven, S. Blanche, et al. Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype Blood, May 15, 2007; 109(10): 4575 - 4581. [Abstract] [Full Text] [PDF] Q.-L. Hao, A. A. George, Y. Zhu, L. W. Barsky, E. Zielinska, J. Cormano, and G. M. Crooks Human Thymus Contains Hematopoietic Stem and Lymphoid Progenitor Populations That Can Be Identified by Differential Expression of CD7. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 1660 - 1660. [Abstract] [PDF] M. Garcia-Peydro, V. G. de Yebenes, and M. L. Toribio Notch1 and IL-7 Receptor Interplay Maintains Proliferation of Human Thymic Progenitors while Suppressing Non-T Cell Fates J. Immunol., September 15, 2006; 177(6): 3711 - 3720. [Abstract] [Full Text] [PDF]

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