DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time 英文参考文献.docVIP

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DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time 英文参考文献.doc

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DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time 英文参考文献

DNAMethylationDynamicsinHumanInduced PluripotentStemCellsoverTime KoichiroNishino,MasashiToyoda,MayuYamazaki-Inoue,YoshihiroFukawatase,EmiChikazawa, HironariSakaguchi,HidenoriAkutsu,AkihiroUmezawa* DepartmentofReproductiveBiology,NationalInstituteforChildHealthandDevelopment,Tokyo,Japan Abstract Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell) and five human embryonic stem cell (ESC) lines, and we followed the aberrant methylation sites in iPSCs for up to 42 weeks. The iPSCs exhibiteddistinctepigeneticdifferencesfromESCs,whichwerecausedbyaberrantmethylationatearlypassages.Multiple appearances and then disappearances of random aberrant methylation were detected throughoutiPSC reprogramming. Continuous passaging of the iPSCs diminished the differences between iPSCs and ESCs, implying that iPSCs lose the characteristics inherited from the parent cells and adapt to very closely resemble ESCs over time. Human iPSCs were graduallyreprogrammedthroughthe‘‘convergence’’ofaberranthyper-methylationeventsthatcontinuouslyappearedina denovomanner.ThisiPSreprogrammingconsistedofstochasticdenovomethylationandselection/fixationofmethylation inanenvironmentsuitableforESCs.Takentogether,randommethylationandconvergencearedrivingforcesforlong-term reprogrammingofiPSCstoESCs. Citation:NishinoK,ToyodaM,Yamazaki-InoueM,FukawataseY,ChikazawaE,etal.(2011)DNAMethylationDynamicsinHumanInducedPluripotentStemCells overTime.PLoSGenet7(5):e1002085.doi:10.1371/journal.pgen.1002085 Editor:JohnM.Greally,AlbertEinsteinCollegeofMedicine,UnitedStatesofAmerica ReceivedDecember2,2010;AcceptedApril1,2011;PublishedMay26,2011 Copyright: ? 2011 Nishino et al. This is an open-access article distributed under the terms of the Creative Comm