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.
CONCLUSION: 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.