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 Jun:77:103409. doi: 10.1016/j.scr.2024.103409. Epub 2024 Mar 29.

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.

MeSH terms

  • CRISPR-Cas Systems* / genetics
  • Cardiomyopathy, Dilated* / genetics
  • Cardiomyopathy, Dilated* / pathology
  • Cell Differentiation
  • Cell Line
  • Filamins* / genetics
  • Filamins* / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Male
  • Mutation

Substances

  • Filamins
  • FLNC protein, human