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dc.contributor.authorWang, Gangen_US
dc.contributor.authorMcCain, Megan L.en_US
dc.contributor.authorYang, Luhanen_US
dc.contributor.authorHe, Aibinen_US
dc.contributor.authorPasqualini, Francesco Silvioen_US
dc.contributor.authorAgarwal, Ashutoshen_US
dc.contributor.authorYuan, Hongyanen_US
dc.contributor.authorJiang, Daweien_US
dc.contributor.authorZhang, Donghuien_US
dc.contributor.authorZangi, Lioren_US
dc.contributor.authorGeva, Judithen_US
dc.contributor.authorRoberts, Amy E.en_US
dc.contributor.authorMa, Qingen_US
dc.contributor.authorDing, Jianen_US
dc.contributor.authorChen, Jinghaien_US
dc.contributor.authorWang, Da-zhien_US
dc.contributor.authorLi, Kaien_US
dc.contributor.authorWang, Jiwuen_US
dc.contributor.authorWanders, Ronald J. A.en_US
dc.contributor.authorKulik, Wimen_US
dc.contributor.authorVaz, Frédéric M.en_US
dc.contributor.authorLaflamme, Michael A.en_US
dc.contributor.authorMurry, Charles E.en_US
dc.contributor.authorChien, Kenneth R.en_US
dc.contributor.authorKelley, Richard I.en_US
dc.contributor.authorChurch, George M.en_US
dc.contributor.authorParker, Kevin Kiten_US
dc.contributor.authorPu, William T.en_US
dc.date.accessioned2015-01-05T18:26:01Z
dc.date.issued2014en_US
dc.identifier.citationWang, G., M. L. McCain, L. Yang, A. He, F. S. Pasqualini, A. Agarwal, H. Yuan, et al. 2014. “Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies.” Nature medicine 20 (6): 616-623. doi:10.1038/nm.3545. http://dx.doi.org/10.1038/nm.3545.en
dc.identifier.issn1078-8956en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581022
dc.description.abstractStudying monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combine patient-derived and genetically engineered iPSCs with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene Tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural, and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS “heart on chip” tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies, and advances iPSC-based in vitro modeling of cardiomyopathy.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nm.3545en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172922/pdf/en
dash.licenseLAAen_US
dc.titleModeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologiesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature medicineen
dash.depositing.authorYang, Luhanen_US
dc.date.available2015-01-05T18:26:01Z
dc.identifier.doi10.1038/nm.3545*
dash.authorsorderedfalse
dash.contributor.affiliatedParker, Kevin
dash.contributor.affiliatedYang, Luhan
dash.contributor.affiliatedPasqualini, Francesco
dash.contributor.affiliatedPu, William
dash.contributor.affiliatedChurch, George


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