Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies

DSpace/Manakin Repository

Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies

Citable link to this page

 

 
Title: Modeling the mitochondrial cardiomyopathy of Barth syndrome with iPSC and heart-on-chip technologies
Author: Wang, Gang; McCain, Megan L.; Yang, Luhan; He, Aibin; Pasqualini, Francesco Silvio; Agarwal, Ashutosh; Yuan, Hongyan; Jiang, Dawei; Zhang, Donghui; Zangi, Lior; Geva, Judith; Roberts, Amy E.; Ma, Qing; Ding, Jian; Chen, Jinghai; Wang, Da-zhi; Li, Kai; Wang, Jiwu; Wanders, Ronald J. A.; Kulik, Wim; Vaz, Frédéric M.; Laflamme, Michael A.; Murry, Charles E.; Chien, Kenneth R.; Kelley, Richard I.; Church, George M.; Parker, Kevin Kit; Pu, William T.

Note: Order does not necessarily reflect citation order of authors.

Citation: Wang, 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.
Full Text & Related Files:
Abstract: Studying 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.
Published Version: doi:10.1038/nm.3545
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172922/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13581022
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters