Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genomic editing of pathogenic TNNI3 mutation in restrictive cardiomyopathy rescues diastolic dysfunction of human induced pluripotent stem cell-derived cardiomyocytes

ABSTRACT: To investigate the physiological characteristics of cardiomyocytes (CM) in restrictive cardiomyopathy (RCM), we established RCM(heterozygous)-iPSC and produced RCM(homozygous)-iPSC and corrected Isogenic-iPSC using CRISPER-CAS9 technology. Then, we used the RNA-seq data obtained from these three iPSCs and three different healthy iPSC-derived CMs for gene expression profiling analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240775 | GEO | 2023/08/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Therapeutic base editing alleviates restrictive cardiomyopathy

Project description:Restrictive cardiomyopathy (RCM) is a severe cardiac disorder characterized by impaired ventricular filling and diastolic dysfunction, with mutations in sarcomeric proteins representing major causative factors. Mutations of TNNI3 gene (e.g. p.R192H) constitute major genetic causes of RCM, particularly affecting pediatric patients and being associated with poor prognosis. Here, we demonstrate that adenine base editor (ABE) is able effectively correct RCM-causing mutation and alleviate RCM in a murine model. We first developed a novel murine model harboring the Tnni3R193H mutation that recapitulates the hallmark features of human RCM. Importantly, targeted delivery of ABE via adeno-associated virus (AAV) achieved efficient and precise correction of the Tnni3R193H mutation in adult RCM mice, leading to significant improvement of cardiac functions. Our findings establish base editing as a therapeutic strategy for RCM and highlight its broader potential for treating genetic cardiomyopathies in clinical settings.

2025-04-30 | GSE295799 | GEO

Pediatric Restrictive Cardiomyopathy Mutation Analysis

Project description:Pediatric Restrictive Cardiomyopathy Mutation Analysis

| PRJNA1197576 | ENA

Pediatric Restrictive Cardiomyopathy Mutation Analysis

Project description:Pediatric Restrictive Cardiomyopathy Mutation Analysis

| PRJNA1197578 | ENA

Therapeutic base editing alleviates restrictive cardiomyopathy

Project description:Therapeutic base editing alleviates restrictive cardiomyopathy

| PRJNA1256393 | ENA

Genomic editing of pathogenic TNNI3 mutation in restrictive cardiomyopathy rescues diastolic dysfunction of human induced pluripotent stem cell-derived cardiomyocytes

Project description:Genomic editing of pathogenic TNNI3 mutation in restrictive cardiomyopathy rescues diastolic dysfunction of human induced pluripotent stem cell-derived cardiomyocytes

| PRJNA1005230 | ENA

Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy

Project description:Purpose: LMNA-DCM accounts for 5-10% of DCM cases and has an age-related penetrance whose onset typically appears between the ages of 30 and 40. However, the precise mechanisms linking the LMNA mutation to increased arrhythmogenicity are still unknown. Methods: We utilized human iPSC-CMs, hESC-CMs, and cardiac tissues with RNA-seq, ChIP-seq, and ATAC-seq technologies. Results: The electrophysiological studies of iPSC-CMs identify the LMNA mutation as a cause of increased arrhythmogenicity in mutant iPSC-CMs through abnormal calcium homeostasis. We find that the mutations in LMNA disrupt the global chromatin conformation, resulting in hyper-activation of the platelet-derived growth factor (PDGF) signaling pathway in LMNA-mutant iPSC-CMs. Inhibition of the PDGF signaling pathway can rescue the arrhythmic phenotype of mutant iPSC-CMs. Conclusions: These findings were corroborated in cardiac tissues from healthy and LMNA-DCM patients, thus confirming a novel mechanism of LMNA-DCM pathogenesis both in vitro and in vivo.

2020-07-17 | GSE101514 | GEO

Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy [ChIP-seq]

Project description:Purpose: LMNA-DCM accounts for 5-10% of DCM cases and has an age-related penetrance whose onset typically appears between the ages of 30 and 40. However, the precise mechanisms linking the LMNA mutation to increased arrhythmogenicity are still unknown. Methods: We utilized human iPSC-CMs RNA-seq, ChIP-seq, and ATAC-seq technologies. Results: The electrophysiological studies of iPSC-CMs identify the LMNA mutation as a cause of increased arrhythmogenicity in mutant iPSC-CMs through abnormal calcium homeostasis. We find that the mutations in LMNA disrupt the global chromatin conformation, resulting in hyper-activation of the platelet-derived growth factor (PDGF) signaling pathway in LMNA-mutant iPSC-CMs. Inhibition of the PDGF signaling pathway can rescue the arrhythmic phenotype of mutant iPSC-CMs. Conclusions: These findings were corroborated in cardiac tissues from healthy and LMNA-DCM patients, thus confirming a novel mechanism of LMNA-DCM pathogenesis both in vitro and in vivo.

2019-07-05 | GSE118884 | GEO

Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy [ATAC-seq]

Project description:Purpose: LMNA-DCM accounts for 5-10% of DCM cases and has an age-related penetrance whose onset typically appears between the ages of 30 and 40. However, the precise mechanisms linking the LMNA mutation to increased arrhythmogenicity are still unknown. Methods: We utilized human iPSC-CMs RNA-seq, ChIP-seq, and ATAC-seq technologies. Results: The electrophysiological studies of iPSC-CMs identify the LMNA mutation as a cause of increased arrhythmogenicity in mutant iPSC-CMs through abnormal calcium homeostasis. We find that the mutations in LMNA disrupt the global chromatin conformation, resulting in hyper-activation of the platelet-derived growth factor (PDGF) signaling pathway in LMNA-mutant iPSC-CMs. Inhibition of the PDGF signaling pathway can rescue the arrhythmic phenotype of mutant iPSC-CMs. Conclusions: These findings were corroborated in cardiac tissues from healthy and LMNA-DCM patients, thus confirming a novel mechanism of LMNA-DCM pathogenesis both in vitro and in vivo.

2019-07-05 | GSE118883 | GEO

Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy [RNA-seq]

Project description:Purpose: LMNA-DCM accounts for 5-10% of DCM cases and has an age-related penetrance whose onset typically appears between the ages of 30 and 40. However, the precise mechanisms linking the LMNA mutation to increased arrhythmogenicity are still unknown. Methods: We utilized human iPSC-CMs RNA-seq, ChIP-seq, and ATAC-seq technologies. Results: The electrophysiological studies of iPSC-CMs identify the LMNA mutation as a cause of increased arrhythmogenicity in mutant iPSC-CMs through abnormal calcium homeostasis. We find that the mutations in LMNA disrupt the global chromatin conformation, resulting in hyper-activation of the platelet-derived growth factor (PDGF) signaling pathway in LMNA-mutant iPSC-CMs. Inhibition of the PDGF signaling pathway can rescue the arrhythmic phenotype of mutant iPSC-CMs. Conclusions: These findings were corroborated in cardiac tissues from healthy and LMNA-DCM patients, thus confirming a novel mechanism of LMNA-DCM pathogenesis both in vitro and in vivo.

2019-07-05 | GSE118882 | GEO

Mislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3

Project description:First, we compared gene expression and alternative splicing changes between differentially-localized P633L-RBM20, WT-RBM20, and R634Q-RBM20 in iPSC-CMs. Using ICS, we sorted iPSC-CMs with differentially-localized RBM20 based on correlation with nuclear staining. This was followed by RNA-sequencing of the sorted populations. Second, we analysed gene expression and splicing changes in iPSC-CMs overexpressing of WT-, R634Q-, or NLS-tagged R634Q-RBM20 in splice deficient cells carrying the homozygous frameshift mutation (S635FS). Third, we performed RNA sequencing of our HeLa Tet:Cas9 eGFP-RBM20-WT and -R634Q to compare their gene expression to iPSC-CMs. Lastly, we performed two genome-wide CRISPR ICS screens in HeLa cells stably expressing eGFP-RBM20-WT and -R634Q, and TetO-Cas9, to identify genes essential for RBM20 nuclear import.

2023-06-19 | GSE220833 | GEO

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