Distinct Roles of MicroRNA-1 and -499 in Ventricular Specification and Functional Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes 英文参考文献.docVIP

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Distinct Roles of MicroRNA-1 and -499 in Ventricular Specification and Functional Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes 英文参考文献.doc

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Distinct Roles of MicroRNA-1 and -499 in Ventricular Specification and Functional Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes 英文参考文献

DistinctRolesofMicroRNA-1and-499inVentricular SpecificationandFunctionalMaturationofHuman EmbryonicStemCell-DerivedCardiomyocytes Ji-DongFu1,StephanieN.Rushing1,2,DeborahK.Lieu1,2,CamieW.Chan1,3,4,Chi-WingKong3,6,7 ,Lin Geng6,KitchenerD.Wilson8,NipavanChiamvimonvat1,KennethR.Boheler6,9,JosephC.Wu8 ,Gordon Keller10,RogerJ.Hajjar2,RonaldA.Li1,2,3,5,6,7* 1UniversityofCaliforniaSchoolofMedicine,Davis,California,UnitedStatesofAmerica,2CenterofCardiovascularResearch,MountSinaiSchoolofMedicine,NewYork, NewYork,UnitedStatesofAmerica,3DepartmentofMedicine,TheUniversityofHongKong,HongKong,4DepartmentofAnatomy,TheUniversityofHongKong,Hong Kong,5DepartmentofPhysiology,TheUniversityofHongKong,HongKong,6StemCellandRegenerativeMedicineConsortium,TheUniversityofHongKong,Hong Kong,7Heart,Brain,HormoneandHealthyAgingResearchCenter,LKSFacultyofMedicine,TheUniversityofHongKong,HongKong,8DepartmentsofMedicineand Radiology,StanfordUniversity,PaloAlto,California,UnitedStatesofAmerica,9LaboratoryofCardiovascularScience,NationalInstituteonAging,NationalInstitutesof Health,Baltimore,Maryland,UnitedStatesofAmerica,10McEwenCentralforRegenerativeMedicine,UniversityHealthNetwork,Toronto,Ontario,Canada Abstract Background: MicroRNAs (miRs) negatively regulate transcription and are important determinants of normal heart developmentandheartfailurepathogenesis.Despitethesignificantknowledgegainedinmousestudies,theirfunctional rolesinhuman(h)heartremainelusive. Methods and Results: We hypothesized that miRs that figure prominently in cardiac differentiation are differentially expressedindifferentiating,developing,andterminallymaturehumancardiomyocytes(CMs).Asafirststep,wemapped themiRprofilesofhuman(h)embryonicstemcells(ESCs),hESC-derived(hE),fetal(hF)andadult(hA)ventricular(V)CMs.63 miRs were differentially expressed between hESCs and hE-VCMs. Of these, 29, including the miR-302 and -371/372/373 clusters,wereassociatedwithpluripotencyanduniquelyexpressedinhESCs.OftheremainingmiRsdifferentiallyexpr