Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny.
OBJECTIVE
The Hox gene family of transcription factors is thought to be involved in the regulation of primitive hematopoietic cells, including stem cells and early committed progenitors, and has also been directly implicated in leukemia. To gain further insight into Hox gene-mediated regulation of hematopoiesis, we investigated the expression pattern of representative Hox genes and two of their cofactors, Pbx1 and Meis1, at different stages of murine hematopoiesis.


METHODS
Functionally distinct subpopulations of murine bone marrow (BM) and fetal liver day 14.5 (FL) cells were isolated by flow cytometry, and gene expression of various homeobox-containing genes was assessed by global cDNA amplification technique.


RESULTS
Hox genes were found preferentially expressed in hematopoietic stem cell (HSC)-enriched subpopulations and downregulated following differentiation and maturation. This profile of expression was observed at both adult and fetal stages of hematopoiesis. The Pbx1 and Meis1 genes had important differences in their expression pattern but were both detected in Hox expressing subpopulations. In particular, Meis1 consistently showed an expression profile closely resembling that of Hox genes. Finally, using the in vitro embryonic stem (ES) cell differentiation model to mimic embryonic hematopoiesis, we found coexpression of Hox genes and their cofactors coincided with the appearance of hematopoietic progenitor cells.


CONCLUSIONS
Together, these results further support the notion that Hox genes are involved in the regulation of early hematopoietic cells and provide strong evidence that they are involved in the regulation of hematopoiesis throughout ontogeny.
Pineault
Nicolas
N
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Helgason
Cheryl D
CD
Lawrence
H Jeffrey
HJ
Humphries
R Keith
RK
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human