Hematopoietic stem cells (HSCs) are defined by their potential for extensive self-renewal and differentiation into progenitor cells over long periods of time. These cells have been intensively studied and the results have established many of the basic concepts foundational to the broad field of stem cell biology. Purification methods now permit the behavior of HSCs to be examined directly. This allows questions about the regulation of key features of stem cells to be addressed with unprecedented specificity and hence resolve some of the conundrums inherent to past HSC research. We set out to investigate the nature of HSC subtypes, focusing on how they are affected during ontogeny, as well as the extrinsic regulation of their differentiation, self-renewal, and apoptosis. The studies performed identified phenotypically and molecularly distinct multi-potent hematopoietic cells, how they change during ontogeny, a change in their steel factor concentration dependency following growth factor activation, and the differential effect of external factors on HSC survival, proliferation and self-maintenance. These findings contribute to an improved understanding of the properties of HSCs and their external control mechanisms.