a model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency遗传和表观遗传调控网络模型识别罕见的转录因子诱导多能性的途径.pdfVIP

A Model for Genetic and Epigenetic Regulatory Networks Identifies Rare Pathways for Transcription Factor Induced Pluripotency Maxim N. Artyomov1,2, Alexander Meissner2,3, Arup K. Chakraborty1,4,5,6* 1 Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 2 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 3 Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute, Cambridge, Massachusetts, United States of America, 4 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 5 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 6 Ragon Institute of MGH, MIT, and Harvard, Charlestown, Massachusetts, United States of America Abstract 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. Citation: Artyomov MN, Meissner A, Chakraborty AK (2010) A Model for Genetic and Epigenetic Regulat