Biophysical modulation of cell fate through chromatin remodelling

Abstract

The use of non-lethal stimuli as cell modulators is a growing research area. The use of such strategies enables the control of cell behaviour and phenotype using stimuli that occur within the normal cellular environment. By using these stimuli, is possible to take advantage of their controlled application in benefit of a targeted cell phenotype modification and interfere with fate determination. Osmoregulatory mechanisms are constituted by diversified signalling mechanisms, which share the objective of maintenance of cell integrity and function when an extracellular osmolarity disturbance occurs. Cellular osmoregulation comprises the regulation of cell volume and osmolyte transport and also protein structure and turnover, and genomic integrity. These mechanisms are observed under distinct physiological and pathophysiological scenarios. This work aims to contribute to a better understanding of the relevance of the environmental osmotic modulation on cell physiology and its potential relevance to cell behaviour and phenotype. The hyposmotic modulation described in this work induced differences in the transcriptional process by an increased RNA polymerase II binding to the chromatin. This has been mediated by the intervention of specific transcription factors such as zinc finger proteins to attain a specific RNA polymerase II binding profile. The hyposmotic modulation has the ability to interfere with cell fate determination processes such as reprogramming and transdifferentiation. The potential of interfering with such complex processes has to do with the broad effect of the hyposmotic modulation on cellular signalling molecules (like calcium and adenosine triphosphate), mitochondrial activity and morphology, chromatin structure, epigenetic landscape, alternative splicing events and transcriptional pattern. The area of cellular therapies is growing exponentially and the basic knowledge on cellular behaviour and cellular response to osmotic changes as well as the development of new tools responsive to osmotic changes can have a crucial role for the development of future therapeutic applications.