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Blood, 15 December 2008, Vol. 112, No. 13, pp. 4862-4873. Prepublished online as a Blood First Edition Paper on October 7, 2008; DOI 10.1182/blood-2008-01-136564. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-01-136564v1 112/13/4862    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 Rodrigues, N. P. Articles by Enver, T. Search for Related Content PubMed PubMed Citation Articles by Rodrigues, N. P. Articles by Enver, T. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS GATA-2 regulates granulocyte-macrophage progenitor cell function Neil P. Rodrigues1, Ashleigh S. Boyd1, Cristina Fugazza1, Gillian E. May1, YanPing Guo1, Alex J. Tipping1, David T. Scadden2,3, Paresh Vyas1, and Tariq Enver1 1 Medical Research Council Hematology Unit, Weatherall Institute for Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; 2 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston; and 3 Harvard Stem Cell Institute, Harvard University, Cambridge, MA The zinc finger transcription factor GATA-2 has been implicated in the regulation of hematopoietic stem cells. Herein, we explored the role of GATA-2 as a candidate regulator of the hematopoietic progenitor cell compartment. We showed that bone marrow from GATA-2 heterozygote (GATA-2+/–) mice displayed attenuated granulocyte-macrophage progenitor function in colony-forming cell (CFC) and serial replating CFC assays. This defect was mapped to the Lin–CD117+Sca-1–CD34+CD16/32high granulocyte-macrophage progenitor (GMP) compartment of GATA-2+/– marrow, which was reduced in size and functionally impaired in CFC assays and competitive transplantation. Similar functional impairments were obtained using a RNA interference approach to stably knockdown GATA-2 in wild-type GMP. Although apoptosis and cell-cycle distribution remained unperturbed in GATA-2+/– GMP, quiescent cells from GATA-2+/– GMP exhibited altered functionality. Gene expression analysis showed attenuated expression of HES-1 mRNA in GATA-2–deficient GMP. Binding of GATA-2 to the HES-1 locus was detected in the myeloid progenitor cell line 32Dcl3, and enforced expression of HES-1 expression in GATA-2+/– GMP rectified the functional defect, suggesting that GATA-2 regulates myeloid progenitor function through HES-1. These data collectively point to GATA-2 as a novel, pivotal determinant of GMP cell fate. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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]

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