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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2730-2737. Prepublished online as a Blood First Edition Paper on July 11, 2008; DOI 10.1182/blood-2008-01-133801. This Article Full Text (PDF) All Versions of this Article: blood-2008-01-133801v1 112/7/2730    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 Martin, C. H Articles by Kaufman, D. S Search for Related Content PubMed PubMed Citation Articles by Martin, C. H Articles by Kaufman, D. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 14, 2008 Accepted June 15, 2008 Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood-derived hematopoietic progenitor cells Colin H Martin, Petter S. Woll, Zhenya Ni, Juan Carlos Zuniga-Pflucker, and Dan S Kaufman* Stem Cell Institute and Department of Medicine, University of Minnesota, Minneapolis, MN, United States Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada * Corresponding author; email: kaufm020{at}umn.edu. Hematopoietic progenitor cells derived from human embryonic stem cells (hESCs) develop into diverse mature hematopoietic lineages, including lymphocytes. While functional natural killer (NK) cells can be efficiently generated in vitro from hESC-derived CD34+ cells, studies of T and B cell development from hESCs have been much more limited. Here, we demonstrate that despite expressing functional Notch-1, CD34+ cells from hESCs did not derive T cells when co-cultured with OP9 cells expressing Delta-like 1, or in fetal thymus organ culture. hESC-derived CD34+ cells also did not produce B cells in vitro. In contrast, CD34+ cells isolated from UCB routinely generated T and B cells when cultured in the same conditions. Notably, both undifferentiated hESCs, and sorted hESC-derived populations with hematopoietic developmental potential exhibited constitutive expression of ID family genes and of transcriptional targets of stem cell factor-induced signaling. These pathways both inhibit T cell development and promote NK cell development. Together, these results demonstrate fundamental differences between hESC-derived hematopoietic progenitors and analogous primary human cells. Therefore, hESCs can be more readily supported to differentiate into certain cell types than others, findings that have important implications for derivation of defined lineage-committed populations from hESCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. S. Kaufman Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells Blood, October 22, 2009; 114(17): 3513 - 3523. [Abstract] [Full Text] [PDF] S. L. McKinney-Freeman, O. Naveiras, F. Yates, S. Loewer, M. Philitas, M. Curran, P. J. Park, and G. Q. Daley Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells Blood, July 9, 2009; 114(2): 268 - 278. [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] 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]

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