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
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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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