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Blood, 9 July 2009, Vol. 114, No. 2, pp. 404-414. Prepublished online as a Blood First Edition Paper on April 27, 2009; DOI 10.1182/blood-2008-09-179150. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-09-179150v1 114/2/404    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 CrossRef Google Scholar Articles by Hashimi, S. T. Articles by Lee, B. PubMed PubMed Citation Articles by Hashimi, S. T. Articles by Lee, B. Related Collections Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation Sara T. Hashimi1,*, Jennifer A. Fulcher2,*, Margaret H. Chang2, Lanny Gov1, Shuo Wang1, and Benhur Lee1,2 Departments of 1 Microbiology, Immunology, and Molecular Genetics, and 2 Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California–Los Angeles MicroRNAs (miRNAs, miRs) modulate a multitude of cellular events. Here, we identify functional miRNA-protein networks that regulate human monocyte-derived dendritic cell (MDDC) differentiation. miRNA profiling revealed stage-specific differential expression of 20 miRNAs during days 1, 3, and 5 of MDDC differentiation. To identify and prioritize miRNA-protein networks for functional validation, we developed a target ranking algorithm that incorporates many features of miRNA regulatory networks. This system prioritized miR-21, miR-34a, and their cognate targets WNT1 and JAG1 for functional validation. Inhibition of both miR-21 and miR-34a stalled MDDC differentiation, as quantified by DC-SIGN/CD14 expression ratios, showing cooperative involvement of these miRNAs in MDDC differentiation. We confirmed that the 3' untranslated regions of WNT1 and JAG1 were functional targets of these miRNAs and provide evidence that these targets were translationally suppressed. Significantly, exogenously added Wnt-1 and Jagged-1 also stalled MDDC differentiation, suggesting that miRNA-mediated inhibition of endogenous WNT1 and JAG1 expression was important for proper MDDC differentiation. Finally, inhibition of miR-21 and miR-34a, or addition of Wnt-1 and Jagged-1, led to a decrease in endocytic capacity, a key function of immature DCs. Thus, our novel approach identified and validated some miRNA-protein networks involved in phenotypic and functional MDDC differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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