Programming differentiation potential in mesenchymal stem cells

Cell fate decisions are largely programmed by interactions between multiple layers of regulation of gene expression. Among these, epigenetic states have been extensively examined, mostly in the context of embryonic stem cell differentiation. Recent studies however have focused on understanding chromatin-based mechanisms of differentiation of adult progenitor cells into specific lineages but not others. The results point to the view that promoter DNA methylation patterns are not the primary determinant of gene activation potential and differentiation capacity of mesenchymal stem cells. Post-translational histone modifications on promoters contribute to establishing a permissive state of differentiation, but cannot either, based on current knowledge, predict transcriptional activation outcome. Additional regulatory layers need to be examined to be able to explain cell fate commitment and ultimately predict cell fate.