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. 2024 Dec:81:103536.
doi: 10.1016/j.scr.2024.103536. Epub 2024 Aug 14.

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

Hanne M Boen  1 , Bert Vandendriessche  2 , Jolien Schippers  2 , Laura Rabaut  2 , Aleksandra Nijak-Paeske  2 , Peter Ponsaerts  3 , Emeline M Van Craenenbroeck  4 , Bart Loeys  2 , Maaike Alaerts  2
Affiliations

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

Hanne M Boen et al. Stem Cell Res. 2024 Dec.

Abstract

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.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanne M Boen reports financial support was provided by Research Foundation Flanders (1192420N). Maaike Alaerts and Emeline M. Van Craenenbroeck report financial support was provided by Research Foundation Flanders (G055821N & 1804320N). BL holds a consolidator grant from the European research Council (Genomia- ERC-COG-2017-771945). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Validation of four isogenic hiPSC TTNtv carrying cellines.
See this image and copyright information in PMC

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