Stem cells have long been regarded as undifferentiated cells capable of proliferation, self-renewal, production of a large number of differentiated progeny, and regeneration of tissues. Generally, it has been thought that only embryonic stem cells (ES) are pluripotent, since during early development such plasticity is critical. Indeed, extensive data support this supposition and differentiation of ES cells into a range of cell types has been documented both in vitro and in vivo. By contrast, stem cells in the adult have traditionally been thought to be restricted in their differentiative and regenerative potential to the tissues in which they reside. Examples include liver cells that proliferate following partial hepatectomy, hematopoietic stem cells (HSC) that reconstitute the blood following lethal irradiation, satellite cells that repair damaged skeletal muscle, and keratinocyte precursors that participate in wound healing. In addition to repairing damage, stem cells play a key role in ongoing tissue homeostasis, for example in maintaining the blood and skin throughout life. Invariably the diagrams of the differentiation of adult stem cell progeny have been linear and irreversible, depicting an orderly progression along a well-defined path concluding in a terminally differentiated cell type.

However, this view of adult stem cell potential has been challenged of late. Bone marrow (BM)-derived cells have been shown not only to replenish the blood, but also to contribute to muscle, brain, liver, heart, and the vascular endothelium. Some reports document stem cell movement in the reverse direction, suggesting that muscle or CNS-derived cells can give rise to the blood. Stromal cells in the bone marrow, which are distinct from HSC, have also been shown to yield a multitude of cell types. Although many of these cell fate transitions have been observed following tissue injury, in some cases such transitions between distinct tissue compartments have been documented in the absence of overt tissue damage.