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Blood, 15 January 2006, Vol. 107, No. 2, pp. 492-500. Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-02-0529. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-02-0529v1 107/2/492    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kieusseian, A. Articles by Dubart-Kupperschmitt, A. Search for Related Content PubMed PubMed Citation Articles by Kieusseian, A. Articles by Dubart-Kupperschmitt, A. Related Collections Gene Expression Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Expression of Pitx2 in stromal cells is required for normal hematopoiesis Aurélie Kieusseian, Jalila Chagraoui, Cécile Kerdudo, Philippe-Emmanuel Mangeot, Philip J. Gage, Nicole Navarro, Brigitte Izac, Georges Uzan, Bernard G. Forget, and Anne Dubart-Kupperschmitt From the Institut Cochin, Département d'Hématologie, Paris; Institut National de la Santé et de la Recherche Médicale (INSERM), U567, Paris; Centre National de la Recherche Scientifique (CNRS), UMR 8104, Paris; Université Paris Descartes, Faculté de Médecine René Descartes, UMR-S 8104, Paris, France; INSERM U506, Hôpital Paul Brousse, Villejuif, France; Human Genetics, University of Michigan, Ann Arbor; and Medicine/Genetics, Yale University School of Medicine, New Haven, CT. Although the expression of Pitx2, a bicoid family homeodomain transcription factor, is highly regulated during hematopoiesis, its function during this process was not documented; we thus studied hematopoiesis in Pitx2-null mice. We found that Pitx2–/– embryos display hypoplastic livers with reduced numbers of hematopoietic cells, but these cells had normal hematopoietic potential, as evidenced by colony-forming assays, immature progenitor cell assays, and long-term repopulation assays. Because the microenvironment is also crucial to the development of normal hematopoiesis, we established Pitx2–/– and Pitx2+/+ stromas from fetal liver and studied their hematopoietic supportive capacity. We showed that the frequency of cobblestone area-forming cells was 4-fold decreased when using Pitx2–/– stromal cells compared with Pitx2+/+ stromal cells, whatever the Pitx2 genotype of hematopoietic cells tested in this assay. This defect was rescued by expression of Pitx2 into Pitx2–/– fetal liver stromal cells, demonstrating a major and direct role of Pitx2 in the hematopoietic supportive capacity of fetal liver stroma. Finally, we showed a reduced capacity of MS5 stromal cells expressing Pitx2 RNAi to support human hematopoiesis. Altogether these data showed that Pitx2 has major functions in the hematopoietic supportive capacity of fetal liver and adult bone marrow stromal cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Lagergren, R. Mansson, J. Zetterblad, E. Smith, B. Basta, D. Bryder, P. Akerblad, and M. Sigvardsson The Cxcl12, Periostin, and Ccl9 Genes Are Direct Targets for Early B-cell Factor in OP-9 Stroma Cells J. Biol. Chem., May 11, 2007; 282(19): 14454 - 14462. [Abstract] [Full Text] [PDF] M. A. Keller, S. Addya, R. Vadigepalli, B. Banini, K. Delgrosso, H. Huang, and S. Surrey Transcriptional regulatory network analysis of developing human erythroid progenitors reveals patterns of coregulation and potential transcriptional regulators Physiol Genomics, December 13, 2006; 28(1): 114 - 128. [Abstract] [Full Text] [PDF]

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