Project description:We generated maps of H3K4me1, H3K27ac (enhancers), H3K4me3, Pol II (promoters) and H3K27me3 (repressed chromatin) in the genome of human iPSC-derived cardiomyocytes Differentiation of cardiomyocytes from iPSC followed by ChIP-seq of H3K27ac, H34me1, H327me3, H3K4me3 and PolII
Project description:We generated an interaction map using capture in situ Hi-C in human iPSC-derived cardiomyocytes Differentiation of cardiomyocytes from iPSC followed by capture in situ Hi-C
Project description:To improve the maturity and reduce the heterogeneity of iPSC-cardiomyocytes, we addressed the diversity of iPSC-cardiomyocytes by single-cell RNA sequencing and analyzed in detail about heterogeneity during cardiac maturation process.
Project description:Recent studies in non-human model systems have shown therapeutic potential of modified mRNA (modRNA) treatments for lysosomal storage diseases. Here, we assessed the efficacy of a modRNA treatment to restore the expression of the α-galactosidase (GLA) gene in a human cardiac model generated from induced-pluripotent stem cell-derived from two patients with Fabry disease. In line with the clinical phenotype, cardiomyocytes from Fabry patient’s induced pluripotent stem cells show accumulation of the glycosphinolipid Globotriaosylceramide (GB3), which is an α-galactosidase substrate. Further, the patient-specific cardiomyocytes have significant upregulation of lysosomal associated proteins. Upon modRNA treatment, a subset of lysosomal proteins were partially restored to wildtype levels, implying the rescue of the molecular phenotype associated with the Fabry genotype. Importantly, a significant reduction of GB3 levels was observed in GLA modRNA treated cardiomyocytes demonstrating that α-galactosidase enzymatic activity was restored. Together, our results validate the utility of patient IPSC-derived cardiomyocytes as a model to study disease processes in Fabry disease and the therapeutic potential of GLA modRNA treatment to reduce GB3 accumulation in the heart.
