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Blood, 15 July 2005, Vol. 106, No. 2, pp. 477-484. Prepublished online as a Blood First Edition Paper on April 5, 2005; DOI 10.1182/blood-2004-08-2989. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-08-2989v1 106/2/477    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 Rodrigues, N. P Articles by Scadden, D. T Search for Related Content PubMed PubMed Citation Articles by Rodrigues, N. P Articles by Scadden, D. T Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 2, 2004 Accepted December 22, 2004 Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem cell homeostasis Neil P Rodrigues, Viktor Janzen, Randolf Forkert, David M Dombkowski, Ashleigh S Boyd, Stuart H Orkin, Tariq Enver, Paresh Vyas, and David T Scadden* Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Haematology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Department of Pediatric Oncology, Children's Hospital and the Dana Farber Cancer Institute, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, USA MRC Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom Department of Haematology, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA * Corresponding author; email: scadden.david{at}mgh.harvard.edu. The zinc finger transcription factor GATA-2 plays a fundamental role in generating hematopoietic stem cells in mammalian development. Less well defined is whether GATA-2 participates in adult stem cell regulation, an issue we addressed using GATA-2 heterozygote mice that express reduced levels of GATA-2 in hematopoietic cells. While GATA-2 +/- mice demonstrated decreases in some colony forming progenitors, the most prominent changes were observed within the stem cell compartment. Heterozygote bone marrow had a lower abundance of Lin-c-kit+Sca-1+CD34- cells and performed poorly in competitive transplantation and quantitative week 5 CAFC assays. Furthermore, a stem cell enriched population from +/- marrow was more quiescent and exhibited a greater frequency of apoptotic cells associated with decreased expression of the anti-apoptotic gene Bcl-xL. Yet the self-renewal potential of the +/- stem cell compartment, as judged by serial transplantations, was unchanged. These data indicate compromised primitive cell proliferation and survival in the setting of a lower GATA-2 gene dose without a change in the differentiation or self-renewal capacity of the stem cells that remain. Thus, GATA-2 dose regulates adult stem cell homeostasis, affecting select aspects of adult stem cell function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Huang, L. C. Dore, Z. Li, S. H. Orkin, G. Feng, S. Lin, and J. D. Crispino GATA-2 Reinforces Megakaryocyte Development in the Absence of GATA-1 Mol. Cell. Biol., September 15, 2009; 29(18): 5168 - 5180. [Abstract] [Full Text] [PDF] A. J. Tipping, C. Pina, A. Castor, D. Hong, N. P. Rodrigues, L. Lazzari, G. E. May, S. E. W. Jacobsen, and T. Enver High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle Blood, March 19, 2009; 113(12): 2661 - 2672. [Abstract] [Full Text] [PDF] B.P. 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