Generation of human induced pluripotent stem cell line EURACi006-A and its isogenic gene-corrected line EURACi006-A-1 from an arrhythmogenic cardiomyopathy patient carrying the c.1643delG PKP2 mutation

Viviana Meraviglia; Sravya Ganesh; Christiaan H Arendzen; Christian Freund; Elena Sommariva; Alessandra Rossini; Milena Bellin

doi:10.1016/j.scr.2021.102426

Generation of human induced pluripotent stem cell line EURACi006-A and its isogenic gene-corrected line EURACi006-A-1 from an arrhythmogenic cardiomyopathy patient carrying the c.1643delG PKP2 mutation

Stem Cell Res. 2021 Jul:54:102426. doi: 10.1016/j.scr.2021.102426. Epub 2021 Jun 8.

Authors

Viviana Meraviglia¹, Sravya Ganesh², Christiaan H Arendzen², Christian Freund², Elena Sommariva³, Alessandra Rossini⁴, Milena Bellin⁵

Affiliations

¹ Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: [email protected].
² Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Leiden University Medical Center hiPSC Hotel, Leiden, The Netherlands.
³ Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino IRCCS, Milan, Italy.
⁴ Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy. Electronic address: [email protected].
⁵ Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Biology, University of Padua, 35131 Padua, Italy; Veneto Institute of Molecular Medicine, 35129 Padua, Italy. Electronic address: [email protected].

PMID: 34134068
DOI: 10.1016/j.scr.2021.102426

Abstract

Arrhythmogenic Cardiomyopathy (ACM) is a rare genetic cardiac disease predominantly associated with mutations in genes of the desmosomes and characterized by arrhythmia and fibro-fatty replacement of the myocardium. We generated human induced pluripotent stem cells (hiPSCs) from one patient affected by ACM carrying the heterozygous c.1643delG (p.G548VfsX15) PKP2 mutation and then corrected the mutation using CRISPR/Cas9 technology. Both original and corrected hiPSC lines showed typical morphology of pluripotent cells, expressed pluripotency markers, displayed a normal karyotype, and differentiated towards the three germ layers. This isogenic hiPSC pair can be used to study the role of the c.1643delG PKP2 mutation in vitro.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cardiomyopathies*
Cell Differentiation
Heterozygote
Humans
Induced Pluripotent Stem Cells*
Mutation / genetics
Plakophilins / genetics

Substances

PKP2 protein, human
Plakophilins