Role of frustrations in cell reprogramming

The cell fate transition is a fundamental characteristic of living organisms. By introducing external perturbations, it is possible to artificially intervene in cell fate and trigger cell reprogramming. Revealing the general principle underlying the induced phenotypic reshaping of cell populations remains a central focus in the field of cell biology. In this study, we investigate the energetic and dynamic features of induced cell phenotypic transition from differentiated somatic state to pluripotent state by constructing a Boolean genetic network model. The simulation and experimental results highlight the critical role of genetic frustration in initiating cell fate transitions, although the two ending phenotypic states are typically featured by minimal frustration. In addition, the altered gene expression profiles exhibit a scale-free distribution, suggesting that there exist a small number of critical genes responsible for the cell fate transition. This study provides important insights into the dynamic principles governing effective cell reprogramming caused by artificial or exogenous interventions.