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1、ARTICLEdoi:10.1038/nature12586ReprogramminginvivoproducesteratomasandiPScellswithtotipotencyfeatures11123345Marı´aAbad,LlucMosteiro,CristinaPantoja,MartaCan˜amero,TeresaRayon,InmaculadaOrs,OsvaldoGran˜a,DiegoMegı´as,67381OrlandoDomı´nguez,DoloresMart
2、ı´nez,MiguelManzanares,SagrarioOrtega&ManuelSerranoReprogrammingofadultcellstogenerateinducedpluripotentstemcells(iPScells)hasopenednewtherapeuticopportunities;however,littleisknownaboutthepossibilityofinvivoreprogrammingwithintissues.Hereweshowthatt
3、ransitoryinductionofthefourfactorsOct4,Sox2,Klf4andc-Mycinmiceresultsinteratomasemergingfrommultipleorgans,implyingthatfullreprogrammingcanoccurinvivo.Analysesofthestomach,intestine,pancreasandkidneyrevealgroupsofdedifferentiatedcellsthatexpressthepl
4、uripotencymarkerNANOG,indicativeofinsitureprogramming.Bybonemarrowtransplantation,wedemonstratethathaematopoieticcellscanalsobereprogrammedinvivo.Notably,reprogrammablemicepresentcirculatingiPScellsinthebloodand,atthetranscriptomelevel,theseinvivogen
5、eratediPScellsareclosertoembryonicstemcells(EScells)thanstandardinvitrogeneratediPScells.Moreover,invivoiPScellsefficientlycontributetothetrophectodermlineage,suggestingthattheyachieveamoreplasticorprimitivestatethanEScells.Finally,intraperitonealinj
6、ectionofinvivoiPScellsgeneratesembryo-likestructuresthatexpressembryonicandextraembryonicmarkers.WeconcludethatreprogramminginvivoisfeasibleandconferstotipotencyfeaturesabsentinstandardiPSorEScells.Thesediscoveriescouldberelevantforfutureapplications
7、ofreprogramminginregenerativemedicine.Reprogrammingintopluripotencyremainsanintensefieldofinvesti-concludethattransgeniclinesi4F-Aandi4F-Bcontainafunctional1,2gationthatisprovidingmanyinsightsaboutcellularplasticity.induciblereprogrammingtransgenetha
8、tisexpressedinmosttissuesCellularreprogramminghasbeenachievedundercarefullycontrolledwithoutaffectingtheresidentendogenousgenes.3invitrocultureconditions,whereastheinvivotissuemicroenviron-mentis,inprinciple,conducivetocellulardifferentiationandoppos
