Hematopoietic cell proliferation and differentiation.

Most hematopoietic stem cells are quiescent in the G0 stage of the cell cycle. Certain combinations of hematopoietic growth factors can bind to their cognate receptors on the stem cell surface, shorten the G0 stage of the cell cycle, and stimulate cell division. Hematopoietic growth factors also act on committed progenitors to increase their survival and to amplify maturing populations by stimulating proliferation. Although differentiation is probably determined largely by an intrinsic program, there is evidence that certain receptors expressed on more mature cells can also direct differentiation. This view is still controversial, as is the view that hematopoietic growth factors act merely to prevent apoptosis. Different members of the hematopoietic growth factor family of receptors recruit overlapping sets of tyrosine kinases and share common signal transduction pathways such as Ras. They also directly activate a cytoplasmic class of transcription factors that then translocate to the nucleus. The development of committed hematopoietic progenitor cells into mature effector cells is regulated by "master" transcription factors that recognize motifs in the promoters of many genes that encode lineage-specific proteins.