Hematopoietic Progenitor Cells Derived from Embryonic Stem Cells: Analysis of Gene Expression

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Abstract
Rhesus monkey embryonic stem (ES) cells undergo differentiation in vitro to generate hematopoietic progenitor cells. Our previous studies demonstrated a high degree of similarity in the expression of genes associated with hematopoietic differentiation, homing, and engraftment in CD34(+) and CD34(+)CD38(-) cells from rhesus monkey ES cells and from fresh or cultured bone marrow (BM). In the present study, we compared the expression patterns of cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors (CDIs) in these cells. The expression of genes for cyclins, CDKs, and CDIs was similar among the hematopoietic progenitor cells of different origins, with only minor differences. Differentially expressed genes were also analyzed in CD34(+) lineage-negative cells derived from mouse ES cells and from BM. No difference or totally divergent results were obtained with the latter system, suggesting that this variation may be species specific. We observed, however, that CD34(+) and CD34(+)CD38(-) cells derived from ES cells expressed embryonic epsilon and zeta as well as alpha, beta, and gamma globin genes, whereas no expression of embryonic globins could be detected in the cell preparations from BM. Moreover, erythroblast-enriched CD34(-) cells derived from 4- or 5-week ES cell differentiation cultures also expressed embryonic, fetal, and adult globin genes, with greater beta gene expression, but otherwise were identical to those of the more primitive CD34(+) cells derived from 2-week ES cultures. These latter observations may reflect the presence of heterogeneous cell populations within the cell fractions that were compared, or they may represent variability among ES-cell-derived hematopoietic stem cells.