Abstract
Human embryonic stem (ES) cells provide a unique model for studying the development and function of human tissues. To better understand early development of the hematopoietic lineage, here we use microarray expression analysis to examine the temporal patterns of gene expression in embryoid bodies derived from human ES cells around the time when the definitive hematopoiesis peaks. We use an empirical Bayes hierarchical modeling approach, called EBarrays, to assess each of the possible temporal patterns of gene expression for the 5 time points examined, and correlate those patterns with the emergence of definitive hematopoiesis. We find that several genes known to be associated with early hematopoietic commitment, such as Flk-1 and TAL-1/SCL, are expressed 4-6 days before the peak colony formation cells (CFCs) production. The expression of a distinct group of genes previously identified as important in adult hematopoietic self-renewal (such as PIK3R1, ABCB1/MDR-1, RGS18, IRS1, SENP6/SUMO-1, and Wnt5A etc. correlated with the emergence of definitive hematopoiesis. Novel genes demonstrating the same expression pattern as this group are likely to have critical roles in the development and self-renewal of definitive hematopoietic precursors.
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