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Blood, 1 July 2006, Vol. 108, No. 1, pp. 116-122. Prepublished online as a Blood First Edition Paper on December 8, 2005; DOI 10.1182/blood-2005-06-2245. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-06-2245v1 108/1/116    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 Bijl, J. Articles by Sauvageau, G. Search for Related Content PubMed PubMed Citation Articles by Bijl, J. Articles by Sauvageau, G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 6, 2005 Accepted October 15, 2005 Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells Janet Bijl, Alexander Thompson, Ramiro Ramirez-Solis, Jana Krosl, David G Grier, H J Lawrence, and Guy Sauvageau* Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer (IRIC), Montreal, Quebec, Canada Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer (IRIC), Montreal, Quebec, Canada; Departments of Haematology, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA Child Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom Department of Medicine, VA Medical Center and University of California, University of California, San Francisco, California, USA Laboratory of Molecular Genetics of Stem Cells, Institute for Research in Immunology and Cancer (IRIC), Montreal, Quebec, Canada; Leukemia Cell Bank of Quebec and Division of Hematology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada; Department of Medicine, Universite de Montreal, Montreal, Quebec, Canada * Corresponding author; email: guy.sauvageau{at}umontreal.ca. Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program which determines self-renewal. However, this function cannot be solely attributed to Hoxb4, since Hoxb4-/- mice are viable and have apparently normal HSC pools. Q-PCR analysis showed that Hoxb4-/- c-Kit+ fetal liver cells expressed moderately higher levels of several Hoxb cluster genes than control cells, raising the possibility that normal HSC activity in Hoxb4-/- mice is due to a compensatory upregulation of other Hoxb genes. In this study, we investigated the competitive repopulation potential of HSCs lacking Hoxb4 alone, or in conjunction with eight other Hoxb genes. Our results show that Hoxb4-/- and Hoxb1-b9-/- fetal liver cells retain full competitive repopulation potential, and the ability to regenerate all myeloid and lymphoid lineages examined. Quantitative Hox gene expression profiling in purified c-Kit+ Hoxb1-b9-/- fetal liver cells revealed an interaction between the Hoxa, b and c clusters with variation in expression levels of Hoxa4, -a11 and -c4. Together, these studies show a complex network of genetic interactions between several Hox genes in primitive hematopoietic cells and demonstrate that HSCs lacking up to 30% of the active Hox genes remain fully competent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-L. Hu, E. Passegue, S. Fong, C. Largman, and H. J. Lawrence Evidence that the Pim1 kinase gene is a direct target of HOXA9 Blood, June 1, 2007; 109(11): 4732 - 4738. [Abstract] [Full Text] [PDF]

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