Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Modeling arrhythmogenic cardiomyopathy fattyfibro pathology through the use of PKP2-deficient human iPSC-derived epicardial cells

ABSTRACT: Modeling arrhythmogenic cardiomyopathy fattyfibro pathology through the use of PKP2-deficient human iPSC-derived epicardial cells

PROVIDER: PRJNA1283061 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Modeling arrhythmogenic cardiomyopathy fattyfibro pathology through the use of PKP2-deficient human iPSC-derived epicardial cells

Project description:Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by progressive fatty-fibro replacement of the ventricular myocardium leading to arrhythmias and an increased risk of sudden cardiac death. To date, the cell types and signaling mechanisms involved in fatty-fibro infiltration of the myocardium have yet to be fully resolved. However, given that fatty-fibro replacement is initiated within the subepicardial layer, epicardial cells are predicted to contribute to the development of this pathology. To investigate the epicardial contributions to the development of ACM, we generated human induced pluripotent stem cell (hiPSC) lines from ACM patients harboring either a PKP2 1849C>T or a PKP2 2013delC mutation alongside CRISPR/Cas9 gene-edited isogenic control lines and a PKP2 knockout line. Epicardial cells derived from patient and knockout conditions displayed enhanced epithelial-to-mesenchymal transition characteristics, dysregulated Wnt and interferon signaling, increased lipid accumulation, and an enhanced fibrotic phenotype when converted to epicardial-derived fibroblasts. Transcriptomic analysis revealed upregulation of insulin growth factor 2 (IGF2) in ACM hiPSC-EPCs as well as in human ACM heart tissue. Subsequent treatment with exogenous IGF2 enhanced expression of the adipogenic transcription factors CEBPA and PPARG in hiPSC-EPCs, suggesting insulin growth factor signaling contributes to ACM fatty-fibro remodeling.

2025-09-05 | GSE301005 | GEO

Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy [scRNA-seq]

Project description:We performed single cell RNA sequencing (scRNAseq) on epicardial cells generated from human induced pluripotent stem cells (hiPSCs) of an arrhythmogenic cardiomyopathy patient and their PKP2 reverted isogenic control. The goal of this experiment was to analyze the process of epicardial to fibro-fatty celluar differentiation in diseased cells and compare the cellular transcirptomes of diseased and healthy cells.

2021-06-20 | GSE149331 | GEO

Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy [bulk RNA-seq]

Project description:We performed bulk cell RNA sequencing (RNAseq) on epicardial cells generated from human induced pluripotent stem cells (hiPSCs) of an arrhythmogenic cardiomyopathy patient and their PKP2 reverted isogenic control. The goal of this experiment was to compare the transcriptomes of diseased and healthy cells.

2021-06-20 | GSE152669 | GEO

Desmosomal protein degradation accompanied by desmosomal and adherens junctions protein disarray as underlying causes of PKP2 driven arrhythmogenic cardiomyopathy

Project description:Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive cardiomyopathy. The pathophysiological events are well understood, yet the underlying molecular mechanisms remain undefined. Here, we created a novel research platform comprising of patient originated hiPSC-derived cardiomyocytes bearing a pathological PKP2 mutation (PKP2 c.2013delC/WT), a novel knock-in murine model carrying the equivalent mutation (Pkp2 c.1755delA/WT), and human explanted ACM hearts, to identify disease driving mechanisms. Pkp2 c.1755delA/WT mice displayed reduced desmosomal and adherens junctions protein levels and protein disarray of the intercalated discs in areas of active fibrotic remodeling. These findings were validated in hiPSC-derived cardiomyocytes and human explanted ACM hearts. Led by proteomics data, we demonstrated that the ubiquitin-proteasome system was responsible for the observed desmosomal protein degradation. The research platform presented here provides a strong scientific basis to identify bona fide pathological processes and will aid in the development of potential therapies for the prevention of ACM disease progression.

2023-11-18 | PXD020605 | Pride

Desmosomal protein degradation as underlying causes of arrhythmogenic cardiomyopathy [PKP2 c.1755delA/WT and WT]

Project description:Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive cardiomyopathy. The pathophysiological events are well understood, yet the underlying molecular mechanisms remain undefined. Here we use patient originated hiPSC-derived cardiomyocytes bearing a pathogenic PKP2 mutation (PKP2 c.2013delC/WT), a corresponding knock-in mouse model carrying the equivalent murine mutation (Pkp2 c.1755delA/WT), and human explanted ACM hearts, to identify disease driving mechanisms. Pkp2 c.1755delA/WT mice over time displayed signs of ACM as observed by cardiac dysfunction and pathological remodeling. At a molecular level these mice showed a reduction in desmosomal and adherens junction proteins as well as disarray of the intercalated discs in areas of active fibrotic remodeling. These findings were validated in the mutant hiPSC-derived cardiomyocytes as well as human explanted ACM hearts, indicating both the conservation and relevance of protein degradation in the pathogenesis of the disease. Led by proteomics data, we demonstrated that the ubiquitin-proteasome system was responsible for the observed desmosomal protein degradation. These findings show the importance of appropriate disease modeling and provide means for therapeutic intervention for the prevention of ACM disease progression.

2023-03-23 | GSE199925 | GEO

Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy

Project description:Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy

| PRJNA640316 | ENA

Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy [scRNA-seq]

Project description:Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy [scRNA-seq]

| PRJNA627962 | ENA

Desmosomal protein degradation as underlying causes of arrhythmogenic cardiomyopathy

Project description:Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive cardiomyopathy. The pathophysiological events are well understood, yet the underlying molecular mechanisms remain undefined. Here we use patient originated hiPSC-derived cardiomyocytes bearing a pathogenic PKP2 mutation (PKP2 c.2013delC/WT), a corresponding knock-in mouse model carrying the equivalent murine mutation (Pkp2 c.1755delA/WT), and human explanted ACM hearts, to identify disease driving mechanisms. Pkp2 c.1755delA/WT mice over time displayed signs of ACM as observed by cardiac dysfunction and pathological remodeling. At a molecular level these mice showed a reduction in desmosomal and adherens junction proteins as well as disarray of the intercalated discs in areas of active fibrotic remodeling. These findings were validated in the mutant hiPSC-derived cardiomyocytes as well as human explanted ACM hearts, indicating both the conservation and relevance of protein degradation in the pathogenesis of the disease. Led by proteomics data, we demonstrated that the ubiquitin-proteasome system was responsible for the observed desmosomal protein degradation. These findings show the importance of appropriate disease modeling and provide means for therapeutic intervention for the prevention of ACM disease progression.

2023-03-23 | GSE160289 | GEO

Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy [bulk RNA-seq]

Project description:Epicardial Differentiation Drives Fibro-fatty Remodeling in Arrhythmogenic Cardiomyopathy [bulk RNA-seq]

| PRJNA640043 | ENA

PKP2 Gene Therapy Improves Heart Function and Reduces Mortality in a Pkp2-deficient Mouse Model of Arrhythmogenic Right Ventricular Cardiomyopathy

Project description:PKP2 Gene Therapy Improves Heart Function and Reduces Mortality in a Pkp2-deficient Mouse Model of Arrhythmogenic Right Ventricular Cardiomyopathy

| PRJNA1064591 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data