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1、LETTERdoi:10.1038/nature12322Invivocardiacreprogrammingcontributestozebrafishheartregeneration111112341RuilinZhang,PeidongHan,HongboYang,KunfuOuyang,DerekLee,Yi-FanLin,KarenOcorr,GusonKang,JuChen,421,5DidierY.R.Stainier{,DeborahYelon&NeilC.ChiDespitecurrenttreatmentregimens,heartfailurere
2、mainstheanagewhenthezebrafishhearthascompletedcardiacloopingand11leadingcauseofmorbidityandmortalityinthedevelopedworldcardiacchambercardiomyocyteshavefullydifferentiated,butthezeb-duetothelimitedcapacityofadultmammalianventricularcardio-rafishremainsopticallyclear.Asaresult,4dpfablatedvm
3、hc:mCherry–myocytestodivideandreplaceventricularmyocardiumlostfromNTRventriclesdisplayedstatisticallysignificantreductioninvenCherry1,2ischaemia-inducedinfarct.Hencethereisgreatinteresttoidentifyfluorescenceby24hpostMTZtreatment(hoursposttreatment,hpt)potentialcellularsourcesandstrategies
4、togeneratenewventricular(Fig.1b,SupplementaryFig.2a).ThisrapiddecreaseinvenCherryfluor-3myocardium.Paststudieshaveshownthatfishandamphibiansescencewasaccompaniedbyareductioninventricularsize(Fig.1b,andearlypostnatalmammalianventricularcardiomyocytescanSupplementaryFig.2b)andfunction(fract
5、ionalareachangedecreased4–6proliferatetohelpregenerateinjuredventricles;however,recentfrom42%to16%at24hpt,n55,P50.004;SupplementaryVideos1studieshavesuggestedthatadditionalendogenouscellularsourcesand2;SupplementaryFig.3a–c),leadingtopericardialoedemaand3maycontributetothisoverallventricu
6、larregeneration.Hereweoveralldecreasedbloodcirculation.TUNEL(TdT-mediateddUTPnickhavedeveloped,inthezebrafish(Daniorerio),acombinationofendlabelling)cell-deathassaysrevealedthatthisdecreaseinventricularfluorescentreportertransgenes,geneticfate-mappingstrategiesfunctionandsizewasduetoaninc
7、reaseinventricularcardiomyocyteandaventricle-specificgeneticablationsystemtodiscoverthatdeath(Fig.1f).Conversely,weobservedthattheatriasignificantlydifferentiatedatrialcardiomyocytescantransdifferentiateintoenlarged(SupplementaryFig.2b)andmaintainednormalcontractile