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DNA Torsion-based Model of Cell Fate Phase Transitions

All stem cell fate transitions, including the metabolic reprogramming of stem cells and the somatic reprogramming of fibroblasts into pluripotent stem cells, can be understood from a unified theoretical model of cell fates. Each cell fate transition can be regarded as a phase transition in DNA supercoiling. However, there has been a dearth of quantitative biophysical models to explain and predict the behaviors of these phase transitions. The generalized Ising model is proposed to define such phase transitions. The model predicts that, apart from temperature-induced phase transitions, there exists DNA torsion frequency-induced phase transitions. Major transitions in epigenetic states, from stem cell activation to differentiation and reprogramming, can be explained by such torsion frequency-induced phase transitions, with important implications for regenerative medicine and medical diagnostics in the future.