Stem cell plasticity: Recapping the decade, mapping the future

In slightly more than a decade of stem cell plasticity research, 24 peer-reviewed articles have demonstrated plasticity across organ and/or embryonic lineage boundaries at the single-cell level, with only 1 article showing negative results. These data, taken together with data about reversibility of gene restrictions that have also accumulated during the same period, indicate that postnatal cells, even “terminally differentiated” ones, have a degree of plasticity not appreciated previously. This review looks back at the four known pathways of cell plasticity and at previously described “plasticity principles” of Genomic Completeness, Cellular Uncertainty, Stochasticity of Cell Origin and Fate, relating these to issues of experimental design and discourse that are key to understanding and evaluating plasticity data. Although the physiologic roles played by such plasticity may still be debated, the manipulations of these phenomena for therapeutic or industrial purposes should finally be considered ripe for exploration. For the future, plasticity, indeed all stem cell biology, must be considered as part of a larger web of cell-to-cell and cell-to-matrix interactions that function fully only at the tissue level; thus, the success of stem cell biology necessarily must involve assembling data from cell and molecular biology research into systems of interactions that might be reasonably called “tissue biology.” Interdisciplinary collaborations with complexity and chaos theorists, using mathematical/computer modeling of cell behaviors, will be vital to fully exploring stem cell behaviors in the coming decades.