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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4720-4728. Prepublished online as a Blood First Edition Paper on March 10, 2009; DOI 10.1182/blood-2008-11-190215. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-11-190215v1 113/19/4720    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 Citing Articles via Google Scholar Google Scholar Articles by Velu, C. S. Articles by Grimes, H. L. Search for Related Content PubMed PubMed Citation Articles by Velu, C. S. Articles by Grimes, H. L. Related Collections Hematopoiesis and Stem Cells Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Gfi1 regulates miR-21 and miR-196b to control myelopoiesis Chinavenmeni S. Velu1, Avinash M. Baktula1, and H. Leighton Grimes1 1 Division of Immunobiology, Cincinnati Children's Hospital Medical Center, OH The zinc finger protein growth factor independent-1 (Gfi1) is a transcriptional repressor that is critically required for normal granulocytic differentiation. GFI1 loss-of-function mutations are found in some patients with severe congenital neutropenia (SCN). The SCN-associated GFI1-mutant proteins act as dominant negatives to block granulopoiesis through selective deregulation of a subset of GFI1 target genes. Here we show that Gfi1 is a master regulator of microRNAs, and that deregulated expression of these microRNAs recapitulates a Gfi1 loss-of-function block to granulocyte colony-stimulating factor (G-CSF)–stimulated granulopoiesis. Specifically, bone marrow cells from a GFI1-mutant SCN patient and Gfi1–/– mice display deregulated expression of miR-21 and miR-196B expression. Flow cytometric analysis and colony assays reveal that the overexpression or depletion of either miR induces changes in myeloid development. However, coexpression of miR-21 and miR-196b (as seen in Gfi1–/– mice and a GFI1N382S SCN patient) completely blocks G-CSF–induced granulopoiesis. Thus, our results not only identify microRNAs whose regulation is required during myelopoiesis, but also provide an example of synergy in microRNA biologic activity and illustrate potential mechanisms underlying SCN disease pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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