Generation of four distinct isogenic cell lines with truncating variants in I-band or A-band titin

Truncating variants in TTN (TTNtv) are present in 15–25 % of patients with idiopathic dilated cardiomyopathy. Interestingly, the pathogenicity of TTNtv seems to be linked to their location within the gene. More proximal I-band TTNtv (TTNtvI) harbour less pathogenic potential than distant A-band TTNt...

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Main Authors: Hanne M. Boen, Bert Vandendriessche, Jolien Schippers, Laura Rabaut, Aleksandra Nijak-Paeske, Peter Ponsaerts, Emeline M. Van Craenenbroeck, Bart Loeys, Maaike Alaerts
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506124002344
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Summary:Truncating variants in TTN (TTNtv) are present in 15–25 % of patients with idiopathic dilated cardiomyopathy. Interestingly, the pathogenicity of TTNtv seems to be linked to their location within the gene. More proximal I-band TTNtv (TTNtvI) harbour less pathogenic potential than distant A-band TTNtv (TTNtvA). We created isogenic human induced pluripotent stem cell lines (hiPSC) with TTNtvI and TTNtvA using CRISPR/Cas9, for the investigation of the pathomechanism in hiPSC-derived cardiomyocytes (hiPSC-CMs). Exon 48 (E48), located in the I-band, and exon 357 (E357), located in the A-band were targeted.
ISSN:1873-5061