A Model for Genetic and Epigenetic Regulatory Networks Identifies Rare Pathways for Transcription Factor Induced Pluripotency

With relatively low efficiency, differentiated cells can be reprogrammed to a pluripotent state by ectopic expression of a few transcription factors. An understanding of the mechanisms that underlie data emerging from such experiments can help design optimal strategies for creating pluripotent cells for patient-specific regenerative medicine. We have developed a computational model for the architecture of the epigenetic and genetic regulatory networks which describes transformations resulting from expression of reprogramming factors. Importantly, our studies identify the rare temporal pathways that result in induced pluripotent cells. Further experimental tests of predictions emerging from our model should lead to fundamental advances in our understanding of how cellular identity is maintained and transformed.