Self-Renewal and Pluripotency Acquired through Somatic Reprogramming to Human Cancer Stem Cells 英文参考文献.docVIP

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Self-Renewal and Pluripotency Acquired through Somatic Reprogramming to Human Cancer Stem Cells 英文参考文献.doc

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Self-Renewal and Pluripotency Acquired through Somatic Reprogramming to Human Cancer Stem Cells 英文参考文献

Self-RenewalandPluripotencyAcquiredthrough SomaticReprogrammingtoHumanCancerStemCells ShogoNagata,KunioHirano,MicheleKanemori,Liang-TsoSun,TakashiTada* DepartmentofStemCellEngineering,InstituteforFrontierMedicalSciences,KyotoUniversity,Kyoto,Japan Abstract Humaninducedpluripotentstemcells(iPSCs)arereprogrammedbytransientexpressionoftranscriptionfactorsinsomatic cells. Approximately 1% of somatic cells can be reprogrammed into iPSCs, while the remaining somatic cells are differentially reprogrammed. Here, we established induced pluripotent cancer stem-like cells (iCSCs) as self-renewing pluripotentcellclones.StableiCSClineswereestablishedfromunstableinducedepithelialstemcell(iESC)linesthroughre- platingfollowedbyembryoidbodyformationandserialtransplantation.iCSCssharedtheexpressionofpluripotentmarker geneswithiPSCs,exceptforREX1andLIN28,whileexhibitedtheexpressionofsomaticmarkergenesEMP1andPPARc .iESCs and iCSCs could generate teratomas with high efficiency by implantation into immunodeficient mice. The second iCSCs isolatedfromdissociatedcellsofteratomafromthefirstiCSCswerestablymaintained,showingageneexpressionprofile similar to the first iCSCs. In the first and second iCSCs, transgene-derived Oct4, Sox2, Klf4, and c-Myc were expressed. ComparativeglobalgeneexpressionanalysesdemonstratedthatthefirstiCSCsweresimilartoiESCs,andclearlydifferent fromhumaniPSCsandsomaticcells.IniCSCs,geneexpressionkineticsofthecorepluripotencyfactorandtheMyc-related factor were pluripotent type, whereas the polycomb complex factor was somatic type. These findings indicate that pluripotent tumorigenicity can be conferred on somatic cells through up-regulation of the core pluripotency and Myc- relatedfactors,priortoestablishmentoftheiPSCmolecularnetworkbyfullreprogrammingthroughdown-regulationofthe polycombcomplexfactor. Citation:NagataS,HiranoK,KanemoriM,SunL-T,TadaT(2012)Self-RenewalandPluripotencyAcquiredthroughSomaticReprogrammingtoHumanCancer StemCells.PLoSONE7(11):e48699.doi:10.13