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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1753-1763. Prepublished online as a Blood First Edition Paper on June 19, 2009; DOI 10.1182/blood-2008-12-196196. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-12-196196v1 114/9/1753    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 Starnes, L. M. Articles by Peschle, C. PubMed PubMed Citation Articles by Starnes, L. M. Articles by Peschle, C. Related Collections Hematopoiesis and Stem Cells Phagocytes, Granulocytes, and Myelopoiesis Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression Linda Marie Starnes1,2,*, Antonio Sorrentino3,*, Elvira Pelosi3, Monica Ballarino4, Ornella Morsilli3, Mauro Biffoni3, Simona Santoro3, Nadia Felli3, Germana Castelli3, Maria Laura De Marchis4, Gianfranco Mastroberardino5, Marco Gabbianelli3, Alessandro Fatica4, Irene Bozzoni4, Clara Nervi1,2, and Cesare Peschle6 1 Department of Histology and Medical Embryology, University "La Sapienza," Rome; 2 San Raffaele Biomedical Park Foundation, Rome; 3 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome; Departments of4 Genetics and Molecular Biology and Istituto di Biologia e Patologia Molecolari (IBPM) and 5 Medicine, University "La Sapienza," Rome; and 6 Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, Italy It is generally conceded that selective combinations of transcription factors determine hematopoietic lineage commitment and differentiation. Here we show that in normal human hematopoiesis the transcription factor nuclear factor I-A (NFI-A) exhibits a marked lineage-specific expression pattern: it is upmodulated in the erythroid (E) lineage while fully suppressed in the granulopoietic (G) series. In unilineage E culture of hematopoietic progenitor cells (HPCs), NFI-A overexpression or knockdown accelerates or blocks erythropoiesis, respectively: notably, NFI-A overexpression restores E differentiation in the presence of low or minimal erythropoietin stimulus. Conversely, NFI-A ectopic expression in unilineage G culture induces a sharp inhibition of granulopoiesis. Finally, in bilineage E + G culture, NFI-A overexpression or suppression drives HPCs into the E or G differentiation pathways, respectively. These NFI-A actions are mediated, at least in part, by a dual and opposite transcriptional action: direct binding and activation or repression of the promoters of the β-globin and G-CSF receptor gene, respectively. Altogether, these results indicate that, in early hematopoiesis, the NFI-A expression level acts as a novel factor channeling HPCs into either the E or G lineage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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