This article has been peer reviewed and accepted for publication. It is in production and has not been edited, so may differ from the final published form.
Methylation mechanisms and bio-mechanical effectors controlling cell fate
Mammalian development and cell fate specification are controlled by multiple regulatory mechanisms that interact in a coordinated way to ensure proper regulation of gene expression and spatial restriction, allowing cells to adopt distinct differentiation traits and a terminal phenotype. Cell potency is, for instance, modulated by changes in methylation that are under the control of methyltransferases and Ten-eleven Translocation (TET) enzymes, which establish/erase a phenotype specific methylation pattern along embryo development as well as during mesenchymal to epithelial transition (MET). Cell plasticity is also responsive to extracellular factors such as small molecules that interact with cell fate definition and induce a transient pluripotent state that allows the direct conversion of an adult mature cell into another differentiated cell type. In addition, cell-secreted vesicles emerge as a powerful effector, capable of modifying cell function and phenotype, delivering different signals such as Oct4 and Sox2 mRNAs -implicated in the preservation of pluripotency, thus triggering epigenetic changes in the recipient cells. In parallel, mechanical properties of the cellular microenvironment and 3-D rearrangement can affect both cell potency and differentiation, through dramatic effects on cytoskeleton remodelling and with the involvement of specific mechano-sensing-related pathways.
RD17348 Accepted 02 October 2017
© CSIRO 2017