Postnatal stem cell survival: does the niche, a rare harbor where to resist the ebb tide of differentiation, also provide lineage-specific instructions?

Abstract

Postnatal stem cells regulate the homeostasis of the majority of our tissues. They continuously generate new progenitors and mature, functional cells to replace old cells, which cannot assume the tissue function anymore and are eliminated. Blood, skin, gut mucosa, muscle, cartilage, nerves, cornea, retina, liver, and many other structures are regulated by stem cells. As a result of their ability to produce large numbers of functionally mature cells, postnatal stem cells represent a promising tool for regenerative therapy. Indeed, unmanipulated stem cells or their progeny amplified in vitro are already used in some clinical applications to restore the function of injured or genetically deficient tissues. However, despite our cumulating understanding concerning postnatal stem cells, many aspects of their functionality remain unclear. For instance, in most tissues, we cannot reliably define the phenotype of the postnatal stem cells sustaining its survival. We do not know to which extent the environment surrounding the stem cell-the niche-which is a key actor insuring stem cell self-maintenance, is also implicated in the maintenance of stem cell lineage specificity. Moreover, we have to clarify whether postnatal stem cells are capable of undertaking "transdifferentiation", that is, the conversion of one cell type into another under physiological conditions. Answering these questions should help us to draw a more accurate picture of postnatal stem cell biology and should lead to the design of safe, effective therapies.