title: HOXA4 provides stronger engraftment potential to short-term repopulating cells than HOXB4.
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.
authors.affiliation: 1 Centre de Recherche de l'Hôpital Maisonneuve-Rosemont , Montréal, Québec, Canada .|2 Départment de Microbiologie et Immunologie et, Université de Montréal , Montréal, Québec, Canada .
authors.forename: Marilaine
authors.initials: M
authors.lastname: Fournier
authors.affiliation: 1 Centre de Recherche de l'Hôpital Maisonneuve-Rosemont , Montréal, Québec, Canada .|2 Départment de Microbiologie et Immunologie et, Université de Montréal , Montréal, Québec, Canada .
authors.forename: Charles-Étienne
authors.initials: CÉ
authors.lastname: Lebert-Ghali
authors.affiliation: 1 Centre de Recherche de l'Hôpital Maisonneuve-Rosemont , Montréal, Québec, Canada .|3 Départment de Médecine, Université de Montréal , Montréal, Québec, Canada .
authors.forename: Janetta J
authors.initials: JJ
authors.lastname: Bijl
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation / Q000235:genetics; D005801:Genes, Homeobox; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; C073547:HOXA4 protein, human