Differential Requirement for Utrophin in the Induced Pluripotent Stem Cell Correction of Muscle versus Fat in Muscular Dystrophy Mice 英文参考文献.docVIP

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Differential Requirement for Utrophin in the Induced Pluripotent Stem Cell Correction of Muscle versus Fat in Muscular Dystrophy Mice 英文参考文献.doc

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Differential Requirement for Utrophin in the Induced Pluripotent Stem Cell Correction of Muscle versus Fat in Muscular Dystrophy Mice 英文参考文献

DifferentialRequirementforUtrophinintheInduced PluripotentStemCellCorrectionofMuscleversusFatin MuscularDystrophyMice AmandaJ.Beck1.,JosephM.Vitale1.,QingshiZhao1,JoelS.Schneider1,CoreyChang1,AneelaAltaf1, JenniferMichaels2,MantuBhaumik3,RobertGrange4,DiegoFraidenraich1* 1DepartmentofCellBiologyandMolecularMedicine,UniversityofMedicineandDentistryofNewJersey,NewJerseyMedicalSchool,Newark,NewJersey,UnitedStates ofAmerica,2DepartmentofNeurology,UniversityofMedicineandDentistryofNewJersey,NewJerseyMedicalSchool,Newark,NewJersey,UnitedStatesofAmerica, 3DepartmentofPediatrics,UniversityofMedicineandDentistryofNewJersey,RobertWoodJohnsonMedicalSchool,Piscataway,NewJersey,UnitedStatesofAmerica, 4DepartmentofHumanNutrition,FoodsandExercise,VirginiaPolytechnicInstituteandStateUniversity,Blacksburg,Virginia,UnitedStatesofAmerica Abstract Duchenne muscular dystrophy (DMD) is an incurable degenerative muscle disorder. We injected WT mouse induced pluripotentstemcells(iPSCs)intomdxandmdx:utrophinmutantblastocysts,whicharepredisposedtodevelopDMDwith anincreasingdegreeofseverity(mdx,,,mdx:utrophin).Inmdxchimeras,iPSC-dystrophinwassuppliedtothemuscle sarcolemmatoeffectcorrectionsatmorphologicalandfunctionallevels.Dystrobrevinwasobservedindystrophin-positive and,atalesserextent,utrophin-positiveareas.Inthemdx:utrophinmutantchimeras,althoughiPSC-dystrophinwasalso supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of dystrobrevinindystrophin-andutrophin-negativeareas.Notonlydystrophin-expressingtissuesareaffectedbyiPSCs.Mdx andmdx:utrophinmicehavereducedfat/bodyweightratio,butiPSCinjectionnormalizedthisparameterinbothmdxand mdx:utrophin chimeras, despite the fact that utrophin was compromised in the mdx:utrophin chimeric fat. The results suggest that the presence of utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlightapotential(utrophin-independent)non-cellautonomousrolefo