Generation of a pluripotent stem cell line (UMGi270-A) and a corresponding CRISPR/Cas9 modified isogenic control (UMGi270-A-1) from a patient with sudden onset dilated cardiomyopathy harboring a FLNC p.R2187P mutation

Wiebke Maurer; Sabine Rebs; Steffen Köhne; Hanna Eberl; Bernd Wollnik; Arne Zibat; Katrin Streckfuss-Bömeke

doi:10.1016/j.scr.2024.103409

Generation of a pluripotent stem cell line (UMGi270-A) and a corresponding CRISPR/Cas9 modified isogenic control (UMGi270-A-1) from a patient with sudden onset dilated cardiomyopathy harboring a FLNC p.R2187P mutation

Stem Cell Res. 2024 Mar 29:77:103409. doi: 10.1016/j.scr.2024.103409. Online ahead of print.

Authors

Wiebke Maurer¹, Sabine Rebs², Steffen Köhne¹, Hanna Eberl², Bernd Wollnik³, Arne Zibat⁴, Katrin Streckfuss-Bömeke⁵

Affiliations

¹ Clinic for Cardiology and Pneumology, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Germany.
² Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
³ Institute of Human Genetics, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Germany; Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells (MBExC), University of Göttingen, Göttingen, Germany.
⁴ Institute of Human Genetics, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Germany.
⁵ Clinic for Cardiology and Pneumology, Georg-August University Göttingen and DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Germany. Electronic address: katrin.streckfuss-boemeke@uni-wuerzburg.de.

PMID: 38583294
DOI: 10.1016/j.scr.2024.103409

Abstract

Filamin C (FLNC) is a highly important actin crosslinker and multi-adaptor protein in striated skeletal and cardiac muscle. Mutations have been linked to a range of cardiomyopathy types. Here, we generated induced pluripotent stem cells (iPSC) from a patient with dilated cardiomyopathy (DCM) harboring a new, unique heterozygous FLNC mutation p.R2187P. From this patient-specific iPSC line, a corresponding isogenic control line was created by CRISPR/Cas9 genome editing. Both, the patient-specific and isogenic-control iPSC maintained full pluripotency, genomic integrity, and in vitro differentiation capacity. All iPSC lines differentiate into iPSC-cardiomyocytes, hence providing the possibility to study the pathogenesis of FLNC-mediated DCM further.