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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1451-1459. Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-08-038901. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-08-038901v1 109/4/1451    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 Chen, Z. Articles by Shivdasani, R. A Search for Related Content PubMed PubMed Citation Articles by Chen, Z. Articles by Shivdasani, R. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 1, 2006 Accepted September 25, 2006 Expression analysis of primary mouse megakaryocyte differentiation and its application to identify stage-specific molecular markers and a novel transcriptional target of NF-E2 Zhao Chen, Michael Hu, and Ramesh A Shivdasani* Harvard Medical School Dana-Farber Cancer Institute Brigham & Women's Hospital * Corresponding author; email: ramesh_shivdasani{at}dfci.harvard.edu. Megakaryocyte (MK) differentiation is well described in morphologic terms but its molecular counterparts and the basis for platelet release are incompletely understood. We profiled mRNA expression in populations of primary mouse MKs representing successive differentiation stages. Genes associated with DNA replication are highly expressed in young MKs, in parallel with endomitosis. Intermediate stages are characterized by disproportionate expression of genes associated with the cytoskeleton, cell migration and G-protein signaling, whereas terminally mature MKs accumulate hemostatic factors, including many membrane proteins. We used these expression profiles to extract a reliable panel of molecular markers for MKs of early, intermediate or advanced differentiation, and establish its value using mouse models of defective thrombopoiesis resulting from absence of GATA-1, NF-E2 or tubulin1. Computational analysis of the promoters of late-expressed MK genes identified new candidate targets for NF-E2, a critical transcriptional regulator of platelet release. One such gene encodes the kinase adaptor protein LIMS1/PINCH1, which is highly expressed in MKs and platelets and significantly reduced in NF-E2-deficient cells. Transactivation studies and chromatin immunoprecipitation implicate Lims1 as a direct target of NF-E2 regulation. Attribution of stage-specific genes, in combination with various applications, thus constitutes a powerful way to study MK differentiation and platelet biogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. E. Geddis The regulation of proplatelet production Haematologica, June 1, 2009; 94(6): 756 - 759. [Full Text] [PDF] D. Miranda-Saavedra, S. De, M. W. Trotter, S. A. Teichmann, and B. Gottgens BloodExpress: a database of gene expression in mouse haematopoiesis Nucleic Acids Res., January 1, 2009; 37(suppl_1): D873 - D879. [Abstract] [Full Text] [PDF] P. G. Fuhrken, C. Chen, P. A. Apostolidis, M. Wang, W. M. Miller, and E. T. Papoutsakis Gene Ontology-driven transcriptional analysis of CD34+ cell-initiated megakaryocytic cultures identifies new transcriptional regulators of megakaryopoiesis Physiol Genomics, April 1, 2008; 33(2): 159 - 169. [Abstract] [Full Text] [PDF] Z. Chen, O. Naveiras, A. Balduini, A. Mammoto, M. A. Conti, R. S. Adelstein, D. Ingber, G. Q. Daley, and R. A. Shivdasani The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway Blood, July 1, 2007; 110(1): 171 - 179. [Abstract] [Full Text] [PDF]

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