Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells

J. Bijl, Alexander Thompson, R. Ramirez-Solis, J. Krosl, David Grier, H.J. Lawrence, G. Sauvageau

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell (HSC) populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program that determines self-renewal. However, this function cannot be solely attributed to Hoxb4 because Hoxb4(-/-) mice are viable and have an apparently normal HSC number. Quantitative polymerase chain reaction 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 up-regulation of other Hoxb genes. In this study, we investigated the competitive repopulation potential of HSCs lacking Hoxb4 alone, or in conjunction with 8 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. Quantitative Hox gene expression profiling in purified c-KIt(+) Hoxb1-bg(-/-) 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.
Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalBlood
Volume108
Issue number1
DOIs
Publication statusPublished - 01 Jul 2006

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells'. Together they form a unique fingerprint.

  • Cite this

    Bijl, J., Thompson, A., Ramirez-Solis, R., Krosl, J., Grier, D., Lawrence, H. J., & Sauvageau, G. (2006). Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells. Blood, 108(1), 116-122. https://doi.org/10.1182/blood-2005-06-2245