The in vitro-based discovery and characterization of hematopoietic regulators were of great value in identifying many of the agents active in controlling hematopoiesis. Subsequent in vivo studies have validated most of the information obtained from the in vitro studies, although the in vitro studies proved to be somewhat misleading in predicting which agents would exhibit the greatest quantitative effects in vivo.

Establishing more clearly the actual situation in vivo has required a return to more complex, and often less satisfactory, studies on genetically manipulated whole animals. Of the two possible general approaches, gene inactivation models have proved more informative than transgenic, overexpression models. Each model has raised multiple questions in need of further resolution and the deletion studies have also indicated that other regulators must exist for various lineages, but have yet to be discovered. Of particular interest is the finding from gene inactivation studies that both G-CSF and thrombopoietin are necessary for the maintenance of normal numbers of progenitor cells in multiple lineages, suggesting that each of these lineage-dominant regulators may have broader actions when operating on cells in the stem cell and progenitor cell compartments.