The somatic epigenome can be reprogrammed to a pluri-potent state by a combination of transcription factors.Altering cell fate involves transcription factors coopera-tion,epigenetic reconfi guration,such as DNA methyl...The somatic epigenome can be reprogrammed to a pluri-potent state by a combination of transcription factors.Altering cell fate involves transcription factors coopera-tion,epigenetic reconfi guration,such as DNA methylation and histone modification,posttranscriptional regulation by microRNAs,and so on.Nevertheless,such reprogram-ming is inefficient.Evidence suggests that during the early stage of reprogramming,the process is stochastic,but by the late stage,it is deterministic.In addition to con-ventional reprogramming methods,dozens of small mol-ecules have been identifi ed that can functionally replace reprogramming factors and signifi cantly improve induced pluripotent stem cell(iPSC)reprogramming.Indeed,iPS cells have been created recently using chemical com-pounds only.iPSCs are thought to display subtle genetic and epigenetic variability;this variability is not random,but occurs at hotspots across the genome.Here we dis-cuss the progress and current perspectives in the fi eld.Research into the reprogramming process today will pave the way for great advances in regenerative medicine in the future.展开更多
基金the National Institutes of Health(NS079625 and HD073162 to P.J.).
文摘The somatic epigenome can be reprogrammed to a pluri-potent state by a combination of transcription factors.Altering cell fate involves transcription factors coopera-tion,epigenetic reconfi guration,such as DNA methylation and histone modification,posttranscriptional regulation by microRNAs,and so on.Nevertheless,such reprogram-ming is inefficient.Evidence suggests that during the early stage of reprogramming,the process is stochastic,but by the late stage,it is deterministic.In addition to con-ventional reprogramming methods,dozens of small mol-ecules have been identifi ed that can functionally replace reprogramming factors and signifi cantly improve induced pluripotent stem cell(iPSC)reprogramming.Indeed,iPS cells have been created recently using chemical com-pounds only.iPSCs are thought to display subtle genetic and epigenetic variability;this variability is not random,but occurs at hotspots across the genome.Here we dis-cuss the progress and current perspectives in the fi eld.Research into the reprogramming process today will pave the way for great advances in regenerative medicine in the future.