Mechanical regulation of genome architecture and cell-fate decisions

Landmark experiments in vitro showed that somatic cells can be reprogrammed to stem-cells by the constitutive expression of particular transcription factors. However, in vivo cells naturally exhibit de-differentiation and trans-differentiation programs, thereby suggesting that the signals from the local mechanical microenvironment may be sufficient to induce stem-cell state transitions. In this review, we discuss recent evidence for the biophysical regulation of genome architecture and nuclear programs. We start by discussing the coupling between cellular architecture, genome organization and gene expression. We then review the role of biophysical factors in regulating genome architecture and cell-state transitions. Finally, we discuss the molecular basis of cell-state transitions during nuclear reprogramming. Collectively, we highlight the importance of the mechanical regulation of genome organization on cell-fate decisions.