Embryonic Stem Cells in the Study of Hematopoiesis

The hematopoietic system is a complex mix of stem cells, committed progenitors, and mature effector cells of at least nine different lineages. Although these cells perform very different functions, they arise from a common ancestor, the hematopoietic stem cell (HSC) (1 –8 ). HSCs may be defined functionally by their ability to repopulate a myeloablated host. In order to achieve this, these cells must be capable of both self-renewal and commitment to different cell lineages. It has been suggested that lineage commitment involves the activation of a small subset of “master genes” that then initiate a cascade of events influencing the pattern of gene expression (and thus the phenotype) in the daughter cells (9 –11 ). As consequence of these changes in gene expression, the functional diversity of cell types formed is increased, but the spectrum of lineage potentials for any given progenitor cell is diminished. The processes of lineage commitment and differentiation are regulated by an array of soluble cytokines (12 ) and growth factors (13 –15 ) and by intercellular interactions (16 ).