Generation of a human induced pluripotent stem cell line UGENTi002-A from an arrhythmogenic cardiomyopathy patient carrying the c.817C>T DSP heterozygous variant and isogenic control using CRISPR/Cas9 editing

Laurens Léger; Jeffrey Aalders; Nina Heymans; Kiara Van Acker-Verberckt; Léa De Bleeckere; Paul Coucke; Björn Menten; Barbara Bauce; Libero Vitiello; Alessandra Rampazzo; Martina Calore; Jolanda van Hengel

doi:10.1016/j.scr.2024.103537

Generation of a human induced pluripotent stem cell line UGENTi002-A from an arrhythmogenic cardiomyopathy patient carrying the c.817C>T DSP heterozygous variant and isogenic control using CRISPR/Cas9 editing

Stem Cell Res. 2024 Dec:81:103537. doi: 10.1016/j.scr.2024.103537. Epub 2024 Aug 22.

Affiliations

¹ Medical Cell Biology Research Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, Entrance 37, 9000 Ghent, Belgium.
² Center for Medical Genetics, Ghent University Hospital, and Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
³ Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35122 Padova, Italy.
⁴ Department of Biology, University of Padova, via Ugo Bassi 58B, 35131 Padova, Padova, Italy.
⁵ Department of Biology, University of Padova, via Ugo Bassi 58B, 35131 Padova, Padova, Italy; School of Cardiovascular Disease (CARIM), Faculty of Medicine and Health Science, Maastricht University, Maastricht, the Netherlands.

PMID: 39217685
DOI: 10.1016/j.scr.2024.103537

Abstract

Arrhythmogenic cardiomyopathy is a severe genetic heart muscle disease characterized by fibro-fatty replacement of the myocardium. Pathogenic variants causal for this disease are mainly located in desmosomal genes, including desmoplakin (DSP). Renal epithelial cells were isolated from a patient carrying the heterozygous c.817C>T (p.Q273*, nonsense) pathogenic variant in DSP, and subsequently reprogrammed using the Cytotune®-iPS 2.0 Sendai Reprogramming Kit. An isogenic control line was generated using CRISPR/Cas9 genome editing. The resulting induced pluripotent stem cell lines were characterized and displayed the required traits for in vitro disease modeling.

MeSH terms

Arrhythmogenic Right Ventricular Dysplasia / genetics
Arrhythmogenic Right Ventricular Dysplasia / pathology
CRISPR-Cas Systems* / genetics
Cell Line
Desmoplakins* / genetics
Desmoplakins* / metabolism
Gene Editing*
Heterozygote
Humans
Induced Pluripotent Stem Cells* / metabolism

Substances

Desmoplakins
DSP protein, human