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
Pluripotent cellular models have shown great promise in the study of a number of neurological disorders. Several advantages of using a stem cell model include the potential for cells to derive disease relevant neurona...Pluripotent cellular models have shown great promise in the study of a number of neurological disorders. Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types, providing a system for researchers to monitor disease progression during neurogenesis, along with serving as a platform for drug discovery. A number of stem cell derived models have been employed to establish in ~,itro research models of Huntington＇s disease that can be used to investigate cellular pathology and screen lk^r drug and cell-based therapies. Although some progress has been made, there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved. In this article we review current stem cell models that have been reported, as well as discuss the issues that impair these studies. We also highlight the prospective application of Huntington＇s disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.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.
基金supported by the National Center for Research Resources P51RR165supported by the Office of Research and Infrastructure Program(ORIP)/OD P510D11132+1 种基金supported by the grant awarded by the ORIP/NIH(RR018827)the Atlanta Clinical and Translational Science Institute to AWSC
文摘Pluripotent cellular models have shown great promise in the study of a number of neurological disorders. Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types, providing a system for researchers to monitor disease progression during neurogenesis, along with serving as a platform for drug discovery. A number of stem cell derived models have been employed to establish in ~,itro research models of Huntington＇s disease that can be used to investigate cellular pathology and screen lk^r drug and cell-based therapies. Although some progress has been made, there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved. In this article we review current stem cell models that have been reported, as well as discuss the issues that impair these studies. We also highlight the prospective application of Huntington＇s disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.
