The stem cell continuum: considerations on the heterogeneity and plasticity of marrow stem cells

Traditional models of hematopoiesis have been hierarchical. Recent evidence showing that marrow stem cells are a cycling population and that the hematopoietic phenotype of these cells reversibly changes with cycle transit have suggested a continuum model of stem cell regulators. Studies on marrow cell conversion to lung cells have extended this continuum to cycle-related differentiation into nonhematopoietic stem cells. We postulate that stem cells transiting cell cycle continually change their chromatin structure, thus providing different windows of transcriptional opportunity and a continually changing phenotype. Final outcomes with this continuum model would be determined by the specific chromatin state of the cell and the presence of specific differentiation inducers.