Epigenetic Basis for the Differentiation Potential of Mesenchymal and Embryonic Stem Cells

SUMMARY: Stem cells have the ability to self-renew, and give rise to one or more differentiated cell types. Embryonic stem cells can differentiate into all cell types of the body and have unlimited self-renewal capacity. Somatic stem cells are found in many adult tissues. They have an extensive but finite lifespan and can differentiate into a more restricted range of cell types. Increasing evidence indicates that the multilineage differentiation ability of stem cells is defined by the potential for expression of developmentally regulated transcription factors and of lineage specification genes. Gene expression, or as emphasized here, the potential for gene expression, is largely controlled by epigenetic modifications of DNA (DNA methylation) and chromatin (such as post-translational histone modifications) in the regulatory regions of specific genes. Epigenetic modifications can also influence the timing of DNA replication. We highlight here how mechanisms by which genes are poised for transcription in undifferentiated stem cells are being uncovered through the mapping of DNA methylation profiles on differentiation-regulated promoters and at the genome-wide level, histone modifications, and transcription factor binding. Epigenetic marks on developmentally regulated and lineage specification genes in stem cells seem to define a state of pluripotency.