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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1223-1229. Prepublished online as a Blood First Edition Paper on April 27, 2006; DOI 10.1182/blood-2005-12-008763. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-12-008763v1 108/4/1223    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 Wang, D. Articles by Friedman, A. D. Search for Related Content PubMed PubMed Citation Articles by Wang, D. Articles by Friedman, A. D. Related Collections Hematopoiesis and Stem Cells Phagocytes Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS C/EBP directs monocytic commitment of primary myeloid progenitors Dehua Wang, Jenice D'Costa, Curt I. Civin, and Alan D. Friedman From the Divisions of Pediatric Oncology and Immunology and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD. C/EBP is required for generation of granulocyte-monocyte progenitors, but the subsequent role of C/EBP in myeloid lineage commitment remains uncertain. We transduced murine marrow cells with C/EBP-estradiol receptor (ER) or empty vector and subjected these to lineage depletion just prior to culture in estradiol with myeloid cytokines. This protocol limits biases due to lineage-specific effects on developmental kinetics, proliferation, and apoptosis. Also, lowering the dose of estradiol reduced activated C/EBP-ER to near the physiologic range. C/EBP-ER increased Mac1+/Gr1–/MPO–/low monocytes 1.9-fold while reducing Mac1+/Gr1+/MPOhi granulocytes 2.5-fold at 48 hours, even in 0.01 µM estradiol. This pattern was confirmed morphologically and by quantitative polymerase chain reaction (PCR) assay of lineage markers. To directly assess effects on immature progenitors, transduced cells were cultured for 1 day with and then in methylcellulose without estradiol. A 2-fold increase in monocytic compared with granulocytic colonies was observed in IL-3/IL-6/SCF or GM-CSF, but not G-CSF, even in 0.01 µM estradiol. C/EBP-ER induced PU.1 mRNA, and PU.1-ER stimulated monocytic development, suggesting that transcriptional induction of PU.1 by C/EBP contributes to monopoiesis. A C/EBP variant incapable of zippering with c-Jun did not induce monopoiesis, and a variant unable to bind NF-B p50 stimulated granulopoiesis, suggesting their cooperation with C/EBP during monocytic commitment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. J. Way, H. Dinh, M. R. Keene, K. E. White, F. I. L. Clanchy, P. Lusby, J. Roiniotis, A. D. Cook, A. I. Cassady, D. J. Curtis, et al. The generation and properties of human macrophage populations from hemopoietic stem cells J. Leukoc. Biol., May 1, 2009; 85(5): 766 - 778. [Abstract] [Full Text] [PDF] D. Wang, I. Paz-Priel, and A. D. Friedman NF-{kappa}B p50 Regulates C/EBP{alpha} Expression and Inflammatory Cytokine-Induced Neutrophil Production J. Immunol., May 1, 2009; 182(9): 5757 - 5762. [Abstract] [Full Text] [PDF] A. R. Soliera, M. R. Lidonnici, G. Ferrari-Amorotti, M. Prisco, Y. Zhang, R. V. Martinez, N. J. Donato, and B. Calabretta Transcriptional repression of c-Myb and GATA-2 is involved in the biologic effects of C/EBP{alpha} in p210BCR/ABL-expressing cells Blood, September 1, 2008; 112(5): 1942 - 1950. [Abstract] [Full Text] [PDF] A. Schuler, M. Schwieger, A. Engelmann, K. Weber, S. Horn, U. Muller, M. A. Arnold, E. N. Olson, and C. Stocking The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate Blood, May 1, 2008; 111(9): 4532 - 4541. [Abstract] [Full Text] [PDF] S. Koschmieder, F. D'Alo, H. Radomska, C. Schoneich, J. S. Chang, M. Konopleva, S. Kobayashi, E. Levantini, N. Suh, A. Di Ruscio, et al. CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha Blood, November 15, 2007; 110(10): 3695 - 3705. [Abstract] [Full Text] [PDF] C. Yeamans, D. Wang, I. Paz-Priel, B. E. Torbett, D. G. Tenen, and A. D. Friedman C/EBP{alpha} binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment Blood, November 1, 2007; 110(9): 3136 - 3142. [Abstract] [Full Text] [PDF] H. Schepers, A. T. J. Wierenga, D. van Gosliga, B. J. L. Eggen, E. Vellenga, and J. J. Schuringa Reintroduction of C/EBP{alpha} in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis Blood, August 15, 2007; 110(4): 1317 - 1325. [Abstract] [Full Text] [PDF]

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