Key result
CRISPR/Cas9 yields a human FLNC knockout stem cell line lacking filamin C in differentiated cardiomyocytes.
Why the study?
Truncating FLNC mutations cause dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, but the exact role of FLNC in dilated cardiomyopathy required further understanding.
The newly generated FLNC knockout human embryonic stem cell line provides a novel in vitro model for studying dilated and arrhythmogenic right ventricular cardiomyopathies.
Answers are grounded in this paper and cite their sources.
Provides a human FLNC-null cardiomyocyte model for mechanistic research; leaves open clinical translation pending in vivo validation.
The FLNC gene encodes the sarcomeric protein filamin C which plays a central role in cardiomyocytes. Truncating FLNC mutations (stop or frameshift etc.) also cause dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). To further understand the exact role of FLNC in DCM, we have generated a human FLNC knockout cell line from the original embryonic stem cell line H9 by CRISPR/Cas9 gene editing technology in this study. The establishment cell line WAe009-A-70 have a compound heterozygous 4 bp deletion/13 bp deletion in the exon 1 of FLNC which resulted in a frameshift in the translation of FLNC. No filamin C protein was detected in cardiomyocytes differentiated from this cell line. Moreover, WAe009-A-70 also expressed pluripotency markers, maintained the ability to differentiate into the three germ layers in vitro and had a normal karyotype.
No takes yet. Share an insight, caveat, or question.
Qin et al. (2021) studied Dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. CRISPR/Cas9 gene editing for FLNC knockout was evaluated on Generation and characterization of FLNC knockout hESC line. A human FLNC knockout embryonic stem cell line was successfully generated using CRISPR/Cas9, resulting in no filamin C protein expression in differentiated cardiomyocytes.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: