Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration.[2017][Elife][10.7554eLife.256

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1、1Reciprocalanalysesinzebrafishandmedakarevealthatharnessingthe2immuneresponsepromotescardiacregeneration31,*11,+24Shih-LeiLai,RubénMarín-Juez,PedroLuísMoura,CarstenKuenne,JasonKuanHan11221,*5Lai,AyeleTaddeseTsedeke,StefanGuenther,MarioLooso,DidierY.R.Stainier.617MaxPl

2、anckInstituteforHeartandLungResearch,DepartmentofDevelopmentalGenetics,8BadNauheim,Germany29MaxPlanckInstituteforHeartandLungResearch,ECCPSBioinformaticsanddeep10sequencingplatform,BadNauheim,Germany+11Currentaddress:SchoolofBiochemistry,UniversityofBristol,UK*12Forco

3、rrespondence:ben.s.lai@gmail.com(SL);Didier.Stainier@mpi-bn.mpg.de(DYRS)1314Abstract1516Zebrafishdisplayadistinctabilitytoregeneratetheirheartfollowinginjury.However,17thisabilityisnotsharedbyanotherteleost,themedaka.Inordertoidentifycellularand18molecularbasesforthis

4、difference,weperformedcomparativetranscriptomicanalyses19followingcardiaccryoinjury.Thiscomparisonpointstomajordifferencesinimmunecell20dynamicsbetweenthesemodels.Uponcloserexamination,weobserveddelayedand21reducedmacrophagerecruitmentinmedaka,alongwithdelayedneutroph

5、ilclearance.To22investigatetheroleofimmuneresponsesincardiacregeneration,wedelayedmacrophage23recruitmentinzebrafishandobservedcompromisedneovascularization,neutrophil24clearance,cardiomyocyteproliferationandscarresolution.Incontrast,stimulatingToll-like25receptorsign

6、alinginmedakaenhancedimmunecelldynamicsandpromoted26neovascularization,neutrophilclearance,cardiomyocyteproliferationandscarresolution.27Altogether,thesedataprovidefurtherinsightintothecomplexroleoftheimmuneresponse28duringregeneration,andserveasaplatformtoidentifyand

7、testadditionalregulatorsof29cardiacrepair.3031Keywords:heartregeneration,zebrafish,medaka,macrophage,neutrophil,immune32response,Toll-likereceptor,neovascularization,cardiomyocyteproliferation3334135Introduction3637Heartfailureresultsfromtheinabilityofthehumanhearttor

8、eplenishdamaged38tissueaftermyocardialinfarction(MI),leadingtoanunresolvedscar,tissueremodeling,and39functionalimpairment.Un