Journal of molecular and cellular cardiology · 2026
Biallelic titin truncation disrupts sarcomere assembly and function in patient-derived iPSC cardiomyocytes.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Erdal Magnhild Sekse, Qi Jing, Erusappan Pugazendhi M, Schubert Mario, Koser Franziska, Basson Adelle, Fischer Konstanze, Dzekhtsiarova Yuliya, Mehnert Carola, Poetsch Mareike, Fomin Andrey, Hou Yufeng, Laasmaa Martin, Ugland Hege K, Lunde Ida G, Gautel Mathias, Longman Cheryl, Jungbluth Heinz, Sundnes Joakim, Linke Wolfgang A, Guan Kaomei, Louch William E, Li Jia
Аннотация
Biallelic titin truncation variants (TTNtvs) are linked to severe cardiac and skeletal muscle diseases, due to unclear mechanisms. Using induced pluripotent stem cell-derived cardiomyocytes from a biallelic TTNtv patient with dilated cardiomyopathy, we investigated sarcomere structure/function. Only the longest of the TTNtvs was detected as protein, and this nearly full-length titin was incorporated into the sarcomere. Subtle structural alterations occurred, with shortened A-bands observed in a subset of sarcomeres. Resulting reduction and imbalance of force development was linked to lowered contractility, and many sarcomeres being stretched by their neighbors. Thus, inefficient sarcomere assembly and interaction promotes cardiomyopathy in biallelic TTNtv.