Telomere shortening is a hallmark of genetic cardiomyopathies

著者: Alex Chia Yu Chang, Andrew Chia Hao Chang, Anna Kirillova, Koki Sasagawa, Willis Su, Gerhard Weber, Jue Lin, Vittavat Termglinchan, Ioannis Karakikes, Timon Seeger, Alexandra Dainis, J. Travis Hinson, Jonathan G. Seidman, Christine E. Seidman, John W. Day, Euan A. Ashley, Joseph C. Wu, Helen M. Blau - Proceedings of the National Academy of Sciences, PNAS 2018 被引用: 103

Quantitative FISH (Q-FISH) of single cells revealed that telomeres were significantly reduced by 26% in HCM and 40% in DCM patient CMs in fixed tissue sections compared with CMs from age- and sex-matched healthy controls. In the cardiac tissues of the same patients, telomere shortening was not evident in vascular smooth muscle cells that do not express or require the contractile proteins, an important control. Telomere shortening was recapitulated in DCM and HCM CMs differentiated from patient-derived human-induced pluripotent stem cells (hiPSCs) measured by two independent assays. This study reveals telomere shortening as a hallmark of genetic HCM and DCM and demonstrates that this shortening can be modeled in vitro by using the hiPSC platform, enabling drug discovery.