Cell Type–Specific Transcriptome Analysis Reveals a Major Role for Zeb1 and miR-200b in Mouse Inner Ear Morphogenesis 英文参考文献.docVIP

Cell Type–Specific Transcriptome Analysis Reveals a Major Role for Zeb1 and miR-200b in Mouse Inner Ear Morphogenesis 英文参考文献.doc

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Cell Type–Specific Transcriptome Analysis Reveals a Major Role for Zeb1 and miR-200b in Mouse Inner Ear Morphogenesis 英文参考文献

CellType–SpecificTranscriptomeAnalysisRevealsa MajorRoleforZeb1andmiR-200binMouseInnerEar Morphogenesis RonnaHertzano1*,RanElkon2,KiyotoKurima3,AnnieMorrisson1,Siaw-LinChan1,MichelleSallin1, AndrewBiedlingmaier1,DouglasS.Darling4,AndrewJ.Griffith3,DavidJ.Eisenman1,ScottE.Strome1 1DepartmentofOtorhinolaryngology–HeadandNeckSurgery,UniversityofMaryland,Baltimore,Maryland,UnitedStatesofAmerica,2DivisionofGeneRegulation,The NetherlandsCancerInstitute,Amsterdam,TheNetherlands,3MolecularBiologyandGeneticsSection,OtolaryngologyBranch,NationalInstituteonDeafnessandOther CommunicationDisorders,NationalInstitutesofHealth,Rockville,Maryland,UnitedStatesofAmerica, 4Department ofOralHealthandRehabilitationandCenterfor GeneticsandMolecularMedicine,UniversityofLouisville,Louisville,Kentucky,UnitedStatesofAmerica Abstract Cellularheterogeneityhinderstheextractionoffunctionallysignificantresultsandinferenceofregulatorynetworksfrom wide-scale expression profiles of complex mammalian organs. The mammalian inner ear consists of the auditory and vestibularsystemsthatareeachcomposedofhaircells,supportingcells,neurons,mesenchymalcells,otherepithelialcells, andbloodvessels.Wedevelopedanovelprotocoltosortauditoryandvestibulartissuesofnewbornmouseinnerearsinto theirmajorcellularcomponents.Transcriptomeprofilingofthesortedcellsidentifiedcelltype–specificexpressionclusters. ComputationalanalysisdetectedtranscriptionfactorsandmicroRNAsthatplaykeyrolesindeterminingcellidentityinthe inner ear. Specifically, our analysis revealed the role of the Zeb1/miR-200b pathway in establishing epithelial and mesenchymalidentityintheinnerear.Furthermore,wedetectedamisregulationoftheZEB1pathwayintheinnerearof Twirler mice, which manifest, among other phenotypes, malformations of the auditory and vestibular labyrinth. The associationofmisregulationoftheZEB1/miR-200bpathwaywithauditoryandvestibulardefectsintheTwirlermutantmice uncovers a novel mechanism underlying deafness and balance disorders. Our appr

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