DeficiencyofmicroRNAmiR-34aexpandscellfatepotentialinpluripotentstemcellsYongJinChoi1,†,Chao-PoLin1,*,†,DavideRisso2,†,SeanChen1,MengHowTan3,JinBLi3,YaleiWu4,CaifuChen5,ZhenyuXuan6,ToddMacfarlan7,WeiqunPeng8,SangYongKim9,TerencePSpeed10,andLinHe1,*1DivisionofCellularandDevelopmentalBiology,MCBdepartment,UniversityofCaliforniaatBerkeley,Berkeley,CA94705,USA2DivisionofBiostatistics,SchoolofPublicHealth,UniversityofCaliforniaatBerkeley,Berkeley,CA94720,USA3DepartmentofGenetics,StanfordUniversity,Stanford,CA94305,USA4ThermoFisherScientific,180OysterPointBlvd.,SouthSanFrancisco,CA940805IntegratedDNATechnologies,200ChesapeakeDrive,RedwoodCity,CA94063,USA6DepartmentofMolecularandCellBiology,UniversityofTexasatDallas,800WestCampbellRoad,Richardson,Texas750807TheEuniceKennedyShriverNationalInstituteofChildHealthandHumanDevelopment,theNationalInstitutesofHealth,Bethesda,MD,USA8DepartmentofPhysics,theGeorgeWashingtonUniversity,Washington,DC20052,USA9DepartmentofPathology,NYUSchoolofMedicine,540FirstAve,NewYork,NY10016,USA10DepartmentofStatistics,UniversityofCalifornia,Berkeley,CA94720USA;DepartmentofMathematicsandStatistics,TheUniversityofMelbourne,Parkville,VIC3010AustraliaandBioinformaticsDivision.TheWalterandElizaHallInstituteofMedicalResearch,Parkville,VIC3052AustraliaAbstractEmbryonicstemcellsandinducedpluripotentstemcellshavepluripotentdevelopmentalpotential,efficientlygivingrisetoallembryoniccelltypes,butrarelyextraembryoniclineages(1).Here,weidentifyamicroRNAmiR-34a,whosedeficiencyinmousepluripotentstemcellsexpandstheirdevelopmentalpotentialtogeneratebothembryonicandextra-embryoniclineagesinvitroandinvivo.miR-34a−/−pluripotentstemcellswiththisbidirectionalcellfatepotentialresemble*Correspondenceto:lhe@berkeley.edu(LH)andewcplin@gmail.com(CPL).†Theseauthorscontributedequally.SupplementaryMaterials:MaterialsandMethodsSupplementaryTextFig.S1–S6TablesS1–S6SupplementaryInformationHHSPublicAccessAuthormanuscriptScience.Authormanuscript;availableinPMC2018September1...