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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 19, 2005 Accepted April 14, 2006 C/EBP directs monocytic commitment of primary myeloid progenitors Dehua Wang, Jenice D'Costa, Curt I Civin, and Alan D Friedman* Divisions of Pediatric Oncology and Immunology and Hematopoiesis, Johns Hopkins University, MD, USA * Corresponding author; email: afriedm2{at}jhmi.edu. 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-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 activate 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 hrs, even in 0.01 µM estradiol. This pattern was confirmed morphologically and by quantitative PCR assay of lineage markers. To directly assess effects on immature progenitors, transduced cells were cultured for one day with and then in methylcellulose without estradiol. A 2-fold increase in monocytic compared with granulocytic colonies was observed in IL3/IL6/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? 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