Disease modeling of desmosome-related cardiomyopathy using induced pluripotent stem cell-derived cardiomyocytes

Figure 2 Allele-specific fluorescent labeling of DSG2 captures desmosome dynamics in isogenic induced pluripotent stem cell-derived cardiomyocytes. To establish a model for desmosome imaging, the tdTomato fluorescent reporter was knocked-in at the 3′-terminus of DSG2 in the three established isogenic induced pluripotent stem cells (iPSCs) using genome editing. These isogenic iPSCs carried identical DSG2 alleles comprising intact and knocked-in alleles distinguished by a synonymous single nucleotide variant (indicated as blue line). These iPSC-derived cardiomyocytes enable desmosome imaging and capturing desmosome recovery after adeno-associated virus-mediated replacement of PKP2. HDR: Homology-directed repair; NEHJ: Non-homologous end joining; AAV: Adeno-associated virus; Hetero: Heterozygous mutation.