SEARCH:   Advanced

Blood, 1 May 2007, Vol. 109, No. 9, pp. 3687-3696. Prepublished online as a Blood First Edition Paper on January 18, 2007; DOI 10.1182/blood-2006-10-054676. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-10-054676v1 109/9/3687    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 Magnusson, M. Articles by Karlsson, S. Search for Related Content PubMed PubMed Citation Articles by Magnusson, M. Articles by Karlsson, S. Related Collections Hematopoiesis and Stem Cells Gene Expression Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS HOXA10 is a critical regulator for hematopoietic stem cells and erythroid/megakaryocyte development Mattias Magnusson1,2, Ann C. M. Brun1,2, Noriko Miyake1,2, Jonas Larsson1,2, Mats Ehinger4, Jon Mar Bjornsson1,2, Anton Wutz5, Mikael Sigvardsson2,3, and Stefan Karlsson1,2 1 Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, Lund University Hospital, Lund, Sweden; 2 Lund Strategic Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, Lund, Sweden; 3 Hematopoietic Stem Cell Laboratory, Institute of Laboratory Medicine, Lund University Hospital, Lund, Sweden; 4 Department of Pathology, Lund University Hospital, Lund, Sweden; 5 Whitehead Institute for Biomedical Research, Cambridge, MA The Homeobox (Hox) transcription factors are important regulators of normal and malignant hematopoiesis because they control proliferation, differentiation, and self-renewal of hematopoietic cells at different levels of the hematopoietic hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13 days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10 was dependent on the HOXA10 concentration, because high levels of HOXA10 had no effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid and megakaryocyte development, demonstrating that tight regulation of HOXA10 is critical for normal development of the erythroid and megakaryocytic lineages. The HOXA10-mediated effects on hematopoietic cells were associated with altered expression of genes that govern stem-cell self-renewal and lineage commitment (eg, hepatic leukemia factor [HlF], Dickkopf-1 [Dkk-1], growth factor independent-1 [Gfi-1], and Gata-1). Interestingly, binding sites for HOXA10 were found in HLF, Dkk-1, and Gata-1, and Dkk-1 and Gfi-1 were transcriptionally activated by HOXA10. These findings reveal novel molecular pathways that act downstream of HOXA10 and identify HOXA10 as a master regulator of postnatal hematopoietic development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Haddad, F. Pflumio, I. Vigon, G. Visentin, C. Auvray, S. Fichelson, and S. Amsellem The HOXB4 Homeoprotein Differentially Promotes Ex Vivo Expansion of Early Human Lymphoid Progenitors Stem Cells, February 1, 2008; 26(2): 312 - 322. [Abstract] [Full Text] [PDF] M. Kobayashi and M. Yamamoto Regulation of GATA1 Gene Expression J. Biochem., July 1, 2007; 142(1): 1 - 10. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020