Establishment of Induced Pluripotent Stem Cells from Centenarians for Neurodegenerative Disease Research 英文参考文献.docVIP

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Establishment of Induced Pluripotent Stem Cells from Centenarians for Neurodegenerative Disease Research 英文参考文献.doc

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Establishment of Induced Pluripotent Stem Cells from Centenarians for Neurodegenerative Disease Research 英文参考文献

EstablishmentofInducedPluripotentStemCellsfrom CentenariansforNeurodegenerativeDiseaseResearch TakuyaYagi1,ArifumiKosakai1,DaisukeIto1*,YoheiOkada2,3,WadoAkamatsu2,YoshihiroNihei1, AkiraNabetani4,FuyukiIshikawa4,YasumichiArai5,NobuyoshiHirose5,HideyukiOkano2, NorihiroSuzuki1 1Department of Neurology, School of Medicine, Keio University, Tokyo, Japan, 2Department of Physiology, School of Medicine, Keio University, Tokyo, Japan, 3KanrinmaruProject, School of Medicine, Keio University, Tokyo, Japan, 4Laboratory ofCell Cycle Regulation, Department of Gene Mechanisms,Graduate School of Biostudies,KyotoUniversity,Kyoto,Japan,5DivisionofGeriatricMedicine,DepartmentofInternalMedicine,SchoolofMedicine,KeioUniversity,Tokyo,Japan Abstract Inducedpluripotentstemcell(iPSC)technologycanbeusedtomodelhumandisorders,createcell-basedmodelsofhuman diseases, including neurodegenerative diseases, and in establishing therapeutic strategies. To detect subtle cellular abnormalitiesassociatedwithcommonlate-onsetdiseaseiniPSCs,validcontroliPSCsderivedfromhealthydonorsfreeof seriouslate-onsetdiseasesarenecessary.Here,wereportthegenerationofiPSCsfromfibroblastsobtainedimmediately postmortem from centenarian donors (106- and 109-years-old) who were extremely healthy until an advanced age. The iPSCsweregeneratedusingaconventionalmethodinvolvingOCT4,SOX2,KLF4,andc-MYC,andthendifferentiatedinto neuronal cells using a neurosphere method. The expression of molecules that play critical roles in late-onset neurodegenerative diseases by neurons differentiated from the centenarian-iPSCs was compared to that of neurons differentiatedfromiPSCsderivedfromfamilialAlzheimer’sdiseaseandfamilialParkinson’sdisease(PARK4:triplicationofthe asynucleingene)patients.TheresultsindicatedthatourseriesofiPSCswouldbeusefulinneurodegenerationresearch.The iPSCs we describe, which were derived from donors with exceptional longevity who were presumed to have no serious diseaseriskfactors,wouldbeusefulinlongevityresearcha