Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy-Reference-Cited by-同舟云学术

Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy

Published:2015-08-28 Issue:6251 Volume:349 Page:982-986
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Hinson John T.¹,Chopra Anant²³,Nafissi Navid⁴,Polacheck William J.²³,Benson Craig C.⁵,Swist Sandra⁶,Gorham Joshua⁴,Yang Luhan³⁴,Schafer Sebastian⁷,Sheng Calvin C.⁴,Haghighi Alireza¹⁴⁸,Homsy Jason⁴,Hubner Norbert⁷⁹,Church George³⁴,Cook Stuart A.¹⁰¹¹,Linke Wolfgang A.⁶,Chen Christopher S.²³,Seidman J. G.⁴,Seidman Christine E.¹⁴⁸

Affiliation:

1. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

2. Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.

3. The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.

4. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

5. Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

6. Department of Cardiovascular Physiology, Ruhr University Bochum, MA 3/56 D-44780, Bochum, Germany.

7. Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany.

8. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

9. DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.

10. National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at Royal Brompton and Harefield National Health Service (NHS) Foundation Trust, Imperial College London, London, UK.

11. National Heart Centre and Duke–National University, Singapore, Singapore.

Abstract

A giant disruption of the heart Certain forms of heart failure originate from genetic mutations. Understanding how the culprit mutant proteins alter normal heart function could lead to more effective treatments. One candidate is the giant protein tintin, which is mutated in a subset of patients with dilated cardiomyopathy. Through a combination of patient-derived stem cells, tissue engineering, and gene editing, Hinson et al. found that disease-associated titin mutations disrupt the function of the contractile unit in heart muscle. As a result, the heart does not respond properly to mechanical and other forms of stress. Science , this issue p. 982

Funder

NIH

Howard Hughes Medical Institute

American Heart Association

German Research Foundation

Leducq Foundation

LaDue Fellowship

Sarnoff Foundation

NIHR Cardiovascular Biomedical Research Unit of Royal Brompton

Harefield NHS Foundation Trust

RESBIO Technology Resource for Polymeric Biomaterials

Publisher