Stem Cells: Epigenetic Basis of Differentiation

Abstract

Generation of mature differentiated cells is essential for the treatment of several diseases that depend on cell replacement therapies. With the growing knowledge of transcriptome diversity in cells, increased understanding now exists on the potential to inter-convert a specialized cell type into a differentiated cell of another lineage (transdifferentiation). Transcription in terminally committed cells is controlled by many extracellular and intracellular components and the intrinsic structure and confirmation of the DNA itself (the epigenome). The patterns of these modifications in differentiated cells are generally stable and heritable with characteristic modification patterns reflecting the phenotype they acquire during differentiation. Adult tissue-derived stem or progenitor cells possess inherent traits that result in "commitment" to a particular phenotype, demonstrated by their relatively restricted differentiation capacity. Adult tissue-derived stem cell populations represent a source of cells that would predictably require fewer manipulations to achieve an alternative, differentiated phenotype. By characterising cells with respect to epigenetic patterns, it may be possible to identify stem / progenitor cells that are poised to differentiate towards a particular lineage. Assessing the chromatin compactness at gene promoter regions may assist in identifying mechanisms for inducing cells to adopt a specific phenotype with increased efficiency of differentiation.