HOXA4 provides stronger engraftment potential to short-term repopulating cells than HOXB4

Stem Cells Dev. 2015 Oct 15;24(20):2413-22. doi: 10.1089/scd.2015.0063. Epub 2015 Aug 12.

Abstract

Genes of the HOX4 paralog group have been shown to expand hematopoietic stem cells (HSCs). Endogenous expression of HOXA4 is 10-fold higher than HOXB4 in embryonic primitive hematopoietic cells undergoing self-renewal suggesting a more potent capacity of HOXA4 to expand HSC. In this study, we provide evidence by direct competitive bone marrow cultures that HOXA4 and HOXB4 induce self-renewal of primitive hematopoietic cells with identical kinetics. Transplantation assays show that short-term repopulation by HOXA4-overexpressing multilineage progenitors was significantly greater than HOXB4-overexpressing progenitors in vivo, indicating differences in the sensitivity of the cells to external signals. Small array gene expression analysis showed an increase in multiple Notch and Wnt signaling -associated genes, including receptors and ligands, as well as pluripotency genes, for both HOXA4- and HOXB4-overexpressing cells, which was more pronounced for HOXA4, suggesting that both HOX proteins may assert their affects through intrinsic and extrinsic pathways to induce self-renewal of primitive hematopoietic cells. Thus, HOXA4 increases short-term repopulation to higher levels than HOXB4, which may involve Notch signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / cytology
  • Cell Proliferation / genetics
  • Genes, Homeobox
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / cytology*
  • Homeodomain Proteins / genetics*
  • Humans
  • Signal Transduction / genetics
  • Transcription Factors / genetics*

Substances

  • HOXB4 protein, human
  • Homeodomain Proteins
  • Transcription Factors
  • HOXA4 protein, human