Stem Cells: Units of Development, Units of Regeneration, and Units in Evolution

Stem cells are not only units of biological organization, responsible for the development and the regeneration of tissue and organ systems, but also are units in evolution by natural selection. Stem cells are generally defined as clonogenic cells capable of both self-renewal and multilineage differentiation. Stem cells can be divided into a long-term subset, capable of indefinite self-renewal, as well as a short-term subset that self-renews for a defined interval. Stem cells give rise to non-self renewing oligolineage progenitors, which in turn give rise to progeny that are more restricted in their differentiating potential, and finally to functionally mature cells. The earliest stem cells in ontogeny are totipotent, extending from the zygote to the inner cell mass of the blastocyst; soon thereafter, totipotent stem cells give rise to somatic stem/progenitor cells and primitive germline stem cells. Very little is known of the stages somatic stem cells take between the blastocyst stage and the emergence of tissue and organ-specific stem cells at about the neurula stage. At this stage, the best studied stem cells-those that will form blood-emerge. This review begins with a detailed examination of hematopoietic (blood-forming) stem cells.