Effects of DAPT and Atoh1 Overexpression on Hair Cell Production and Hair Bundle Orientation in Cultured Organ of Corti from Neonatal Rats 英文参考文献.docVIP

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Effects of DAPT and Atoh1 Overexpression on Hair Cell Production and Hair Bundle Orientation in Cultured Organ of Corti from Neonatal Rats 英文参考文献.doc

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Effects of DAPT and Atoh1 Overexpression on Hair Cell Production and Hair Bundle Orientation in Cultured Organ of Corti from Neonatal Rats 英文参考文献

EffectsofDAPTandAtoh1OverexpressiononHairCell ProductionandHairBundleOrientationinCultured OrganofCortifromNeonatalRats Li-DongZhao1.,Wei-WeiGuo1.,ChangLin2.,Li-XianLi1,2.,Jian-HeSun1,NanWu1,Li-LiRen1 ,Xin-Xin Li1,Hui-ZhanLiu1,Wie-YenYoung1,Wei-QiangGao3,4,5*,Shi-MingYang1* 1DepartmentofOtolaryngologyHeadandNeckSurgery,InstituteofOtolaryngology,ChinesePLAGeneralHospital,Beijing,China,2DepartmentofOtolaryngologyHead andNeckSurgery,FirstAffiliatedHospitalofFujianMedicalUniversity,Fuzhou,China,3Renji-MedXClinicalStemCellResearchCenter,RenjiHospital,ShanghaiJiaoTong UniversitySchoolofMedicine,Shanghai,China,4Med-XResearchInstitute,ShanghaiJiaoTongUniversity,Shanghai,China,5ShanghaiCancerInstitute,RenjiHospital, ShanghaiJiaoTongUniversitySchoolofMedicine,Shanghai,China Abstract Background: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanenthearingloss.PreviousstudiesinculturedOrganofCortidissectedfromneonatalanimalshaveshownthatboth DAPT(r-secretaseinhibitorintheNotchsignalpathway)treatmentandAtoh1overexpressioncaninducesupernumerary haircells.TheeffectsofsimultaneousDAPTtreatmentandAtoh1overexpressioninthecellsofculturedOrganofCortifrom neonatalratsarestillobscure. PrincipalFindings:Inthisstudy,wesetouttoinvestigatetheinteractionofDAPTtreatmentandAtoh1overexpressionas wellasculturetimeandthelocationofbasilarfragmentisolatedformneonatalratinnerear.OurresultsshowedthatDAPT treatmentinducedmorehaircellsintheapicalturn,whileAtoh1overexpressioninducedmoreextrahaircellsinthemiddle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the inductionofsupernumeraryhaircellsbybothDAPTandAtoh1overexpressionisdependentonthetreatmenttimeandthe locationofthecochleartissue.Moreover,DAPTtreatmentcausesdramaticchangesintheorientationofthestereociliary bundlesofhaircells,whereasAtoh1overexpressiondidn’tinducedrasticchangeofthepolarityofstereociliarybundles. Conclusio