Telomerase is essential for cardiac differentiation and sustained metabolism of human cardiomyocytes

• DOI: 10.1007/s00018-024-05239-7
• Publication Date: 2024-04-24T18:01:48Z
• Authors: Shambhabi Chatterjee; Megan Leach-Mehrwald; Cheng-Kai Huang; Ke Xiao; Maximilian Fuchs; Mandy Otto; Dongchao Lu; Vinh Dang; Thomas Winkler; Cynthia E. Dunbar; Thomas Thum; Christian Bär
• Keywords: Induced Pluripotent Stem Cells; Humans; Original Article; Myocytes, Cardiac; Cell Differentiation; Telomere; Telomerase; Telomere Shortening; Cell Line

Abstract Telomeres as the protective ends of linear chromosomes, are synthesized by enzyme telomerase (TERT). Critically short telomeres essentially contribute to aging-related diseases and associated with a broad spectrum disorders known telomeropathies. In cardiomyocytes, telomere length is strongly correlated cardiomyopathies but it remains ambiguous whether cause or result disease. this study, we employed an inducible CRISPRi human induced pluripotent stem cell (hiPSC) line silence TERT expression enabling generation hiPSCs hiPSC-derived cardiomyocytes long telomeres. Reduced activity shorter lengths global transcriptomic changes cardiac developmental pathways. Consequently, differentiation potential towards was impaired single RNA sequencing revealed shift more smooth muscle like identity in cells shortest Poor cardiomyocyte function increased sensitivity stress directly extent shortening. Collectively our data demonstrates dependent cardiomyogenic defect, highlighting model powerful platform study mechanisms consequences heart also context