JACC: Basic to Translational Science (Dec 2018)
Novel Adult-Onset Systolic Cardiomyopathy Due to MYH7 E848G Mutation in Patient-Derived Induced Pluripotent Stem Cells
- Kai-Chun Yang, MD,
- Astrid Breitbart, MD,
- Willem J. De Lange, PhD,
- Peter Hofsteen, PhD,
- Akiko Futakuchi-Tsuchida, BS,
- Joy Xu, MSE,
- Cody Schopf, BS,
- Maria V. Razumova, PhD,
- Alex Jiao, PhD,
- Robert Boucek, MD,
- Lil Pabon, PhD,
- Hans Reinecke, PhD,
- Deok-Ho Kim, PhD,
- J. Carter Ralphe, MD,
- Michael Regnier, PhD,
- Charles E. Murry, MD, PhD
Affiliations
- Kai-Chun Yang, MD
- Department of Medicine/Cardiology, University of Washington, Seattle, Washington; Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Astrid Breitbart, MD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Willem J. De Lange, PhD
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
- Peter Hofsteen, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Akiko Futakuchi-Tsuchida, BS
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Joy Xu, MSE
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington
- Cody Schopf, BS
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Maria V. Razumova, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington
- Alex Jiao, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington
- Robert Boucek, MD
- Department of Pediatrics, Seattle’s Children’s Hospital and the University of Washington, Seattle, Washington
- Lil Pabon, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Hans Reinecke, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington
- Deok-Ho Kim, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington
- J. Carter Ralphe, MD
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
- Michael Regnier, PhD
- Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington
- Charles E. Murry, MD, PhD
- Department of Medicine/Cardiology, University of Washington, Seattle, Washington; Center for Cardiovascular Biology, University of Washington, Seattle, Washington; Department of Pathology, University of Washington, Seattle, Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington; Address for correspondence: Dr. Charles E. Murry, Institute for Stem Cell and Regenerative Medicine, University of Washington, 850 Republican Street, Room 453, Brotman Building, Seattle, Washington 98109.
- Journal volume & issue
-
Vol. 3,
no. 6
pp. 728 – 740
Abstract
Summary: A novel myosin heavy chain 7 mutation (E848G) identified in a familial cardiomyopathy was studied in patient-specific induced pluripotent stem cell–derived cardiomyocytes. The cardiomyopathic human induced pluripotent stem cell–derived cardiomyocytes exhibited reduced contractile function as single cells and engineered heart tissues, and genome-edited isogenic cells confirmed the pathogenic nature of the E848G mutation. Reduced contractility may result from impaired interaction between myosin heavy chain 7 and cardiac myosin binding protein C. Key Words: disease-modeling, engineered heart tissue, genetic cardiomyopathy, induced pluripotent stem cells
