DIFFERENTIAL EXPRESSION OF HOMEOBOX GENES IN FUNCTIONALLY DISTINCT CD34(-MARROW CELLS() SUBPOPULATIONS OF HUMAN BONE)

Class I homeobox (Hox) genes encode a major group of transcription fac tors controlling embryonic development and have been implicated in the continuing process of hematopoietic cell differentiation. They are cl ustered on four chromosomes and, in early development, exhibit spatial ly restricted expression with respect to their 3' --> 5' chromosomal p osition. By using an improved PCR-based method for amplifying total cD NA derived from limited cell numbers, we now describe the expression o f class I Hox genes in highly purified CD34(+) cell subpopulations iso lated from normal human bone marrow that represent functionally distin ct stem and progenitor cell compartments. Our data indicate that at le ast 16 different Hox genes, mainly from the A and the B clusters, are expressed in one or more of these subpopulations of human hematopoieti c cells. Moreover, markedly elevated expression of some of the Hox gen es found at the 3' end of the A and B clusters (e.g., HoxB3) was a uni que feature of the subpopulations that contained the most primitive fu nctionally defined cells, whereas genes located in the 5' region of ea ch cluster (e.g., HoxA10) were found to be expressed at nearly equal l evels in the CD34(+) subpopulations analyzed. In contrast to the findi ngs for CD34(+) cells, expression of two selected Hox genes, HoxB3 and HoxA10, was virtually extinguished in the CD34(-)fraction of bone mar row cells. These results demonstrate the expression of a broad range o f Hox genes in primitive hematopoietic cells and point to the existenc e of a regulated program of Hox gene expression during their normal de velopment.