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1、CellStemCellPerspectiveInducedPluripotentStemCells:Past,Present,andFutureShinyaYamanaka1,2,*1CenterforiPSCellResearchandApplication,KyotoUniversity,Kyoto606-8507,Japan2GladstoneInstituteofCardiovascularDisease,SanFrancisco,CA94158,USA*Correspondence:yamanaka@
2、cira.kyoto-u.ac.jpDOI10.1016/j.stem.2012.05.005ThedevelopmentofiPSCsre?ectedthemergingofthreemajorscienti?cstreamsandhasinturnledtoaddi-tionalnewbranchesofinvestigation.However,thereisstilldebateaboutwhetheriPSCsarefunctionallyequivalenttoESCs.Thisquestionsho
3、uldbeansweredonlybyscience,notbypoliticsorbusiness.Introduction1981(EvansandKaufman,1981;Martin,1981),AustinSmithIn2006,weshowedthatstemcellswithpropertiessimilartoandothershaveestablishedcultureconditionsthatenabletheESCscouldbegeneratedfrommouse?broblastsby
4、simulta-long-termmaintenanceofpluripotency(Smithetal.,1988).Aneouslyintroducingfourgenes(TakahashiandYamanaka,keyfactorformaintenanceofmouseESCswasleukemiainhib-2006).WedesignatedthesecellsiPSCs.In2007,wereporteditoryfactor(LIF).Likewise,sincethe?rstgeneratio
5、nofhumanthatasimilarapproachwasapplicableforhuman?broblastsESCs(Thomsonetal.,1998),optimalcultureconditionswithandthatbyintroducingahandfuloffactors,humaniPSCscanbasic?broblastgrowthfactor(bFGF)havebeenestablished.begenerated(Takahashietal.,2007).Onthesameday
6、,JamesCombiningthe?rsttwostreamsofresearchledustohypoth-Thomson’sgroupalsoreportedthegenerationofhumaniPSCesizethatitisacombinationofmultiplefactorsinoocytesorusingadifferentcombinationoffactors(Yuetal.,2007).ESCsthatreprogramsomaticcellsbackintotheembryonics
7、tateandtodesignexperimentstoidentifythatcombination.TheMergingofThreeScienti?cStreamsLedtotheUsinginformationaboutthecultureconditionsthatareneededProductionofiPSCstoculturepluripotentcells,wewerethenabletoidentifyfourLikeanyotherscienti?cadvance,iPSCtechnolo
8、gywasestab-factorsthatcangenerateiPSCs.lishedonthebasisofnumerous?ndingsbypastandcurrentscientistsinrelated?elds.TherewerethreemajorstreamsofMaturationandUnderstandingofiPSCTechnologyrese
