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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1785-1796. Prepublished online as a Blood First Edition Paper on October 28, 2004; DOI 10.1182/blood-2004-08-3346. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2004-08-3346v1 105/4/1785    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 Theilgaard-Monch, K. Articles by Borregaard, N. Search for Related Content PubMed PubMed Citation Articles by Theilgaard-Monch, K. Articles by Borregaard, N. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 27, 2004 Accepted October 18, 2004 The transcriptional program of terminal granulocytic differentiation in man Kim Theilgaard-Monch*, Lars C Jacobsen, Rehannah Borup, Thomas Rasmussen, Malene D Bjerregaard, Finn C Nielsen, Jack Cowland, and Niels Borregaard Department of Hematology, Rigshospitalet, The Granulocyte Research Laboratory, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Hematology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark * Corresponding author; email: kimthei{at}rh.dk. To characterize the transcriptional program that governs terminal granulocytic differentiation in vivo, we performed comprehensive microarray analyses of human bone marrow populations highly enriched in promyelocytes (PMs), myelocytes/metamyelocytes (MYs), and neutrophils (bm-PMNs). These analyses identified 11,310 genes involved in differentiation, of which 6,700 were differentially regulated including previously unidentified effector proteins and surface receptors of neutrophils. Differentiation of PMs towards MYs was accompanied by a marked decline of proliferative and general cellular activity as defined by downregulation of E2F target genes, cyclin dependent kinases 2/4/6, and various metabolic, proteasomal, and mitochondrial genes. Expression patterns of apoptosis genes indicated death control by the p53-pathway in PMs and by death receptor pathways in bm-PMNs. Effector proteins critical for host defense were expressed successively throughout granulocytic differentiation, whereas receptors and receptor ligands essential for the activation of the host defense program were terminally upregulated in bm-PMNs. The upregulation of ligand-receptor pairs, which are defined inducers as well as target genes of NF-B, suggests a constitutive activation of NF-B in bm-PMNs by autocrine loops. Overall, these results define a granulocytic differentiation model governed by a highly coordinated fail-safe program, which promotes completion of differentiation before cells gain responsiveness towards activating stimuli that accompany infections. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A microarray window into granulocyte development and function Alan D. Friedman Blood 2005 105: 1379. [Full Text] [PDF] This article has been cited by other articles: B. Jakiela, W. Szczeklik, B. 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