Establishing a new human hypertrophic cardiomyopathy-specific model using human embryonic stem cells.

Establishing a new human hypertrophic cardiomyopathy-specific model using human embryonic stem cells. Exp Cell Res. 2019 Nov 20;:111736 Authors: Cai H, Li B, Bai A, Huang J, Zhan Y, Sun N, Liang Q, Xu C Abstract Symptom of ventricular hypertrophy caused by cardiac troponin T (TNNT2) mutations is mild, while patients often showed high incidence of sudden cardiac death. The 92nd arginine to glutamine mutation (R92Q) of cTnT was one of the mutant hotspots in hypertrophic cardiomyopathy (HCM). However, there are no such human disease models yet. To solve this problem, we generated TNNT2 R92Q mutant hESC cell lines (heterozygote or homozygote) using TALEN mediated homologous recombination in this study. After directed cardiac differentiation, we found a relative larger cell size in both heterozygous and homozygous TNNT2 R92Q hESC-cardiomyocytes. Expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a) were downregulated, while myocyte specific enhancer factor 2c (MEF2c) and the ratio of beta myosin to alpha myosin heavy chain (MYH7/MYH6) were increased in heterozygous TNNT2 R92Q hESC-cardiomyocytes. TNNT2 R92Q mutant cardiomyocytes exhibited efficient responses to heart-related pharmaceutical agents. We also found TNNT2 R92Q heterozygous mutant cardiomyocytes showed increased calcium sensitivity and contractility. Further, engineered heart tissues (EHTs) prepared b...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research