Characterization of primitive marrow CD34+ cells that persist after a sublethal dose of total body irradiation.

Knowledge of the molecular events that occur during hematopoietic stem/progenitor cell (HSPC) development is vital to our understanding of blood cell production. To study the functional groups of genes characteristic of HSPCs we isolated a subpopulation of CD34 + bone marrow (BM) cells from nonhuman primates that persisted in vivo after a sublethal dose of total body irradiation (TBI). CD34 + cells isolated during the phase of maximal hematopoietic suppression show a transcriptional profile characteristic of metabolically inactive cells, with strong coordinate downregulation of a large number of genes required for protein production and processing. Consistent with this profile, these CD34 + cells were not able to generate hematopoietic colonies. Transcriptional profiling of these CD34 + cells in conjunction with a pathway analysis method reveals several classes of functionally related genes that are upregulated in comparison to the CD34 + cells obtained prior to TBI. These families included genes known to be associated with self-renewal and maintenance of HSPCs (including bone morphogenetic proteins), resistance to apoptosis ( Bcl-2 ) as well as genes characteristic of a variety of nonhematopoietic tissues (gamma-aminobutyric acid/glycine receptor, complement receptor C1qRp ). In contrast, during the period of hematopoietic recovery, the CD34 + cells expressed higher level of genes encoding factors regulating maturation and differentiation of HSPCs. Our data indicate that the primitive BM CD34 + cell population that persists after radiation possesses a transcriptional profile suggestive of pluripotency.