Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118087 | GEO | 2021/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [scRNA-Seq]

Project description:We reported the scRNA-seq of hESC-derived SHOX2+mCherry+ cells and SHOX2-mCherry+ cells

2021-07-01 | GSE119682 | GEO

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [RNA-seq]

Project description:The sinoatrial node (SAN) is the primary pacemaker of the heart. The human SAN is poorly understood due to limited primary tissue access and lack of robust in vitro derivation methods. We developed an efficient strategy, using a dual SHOX2:GFP; MYH6:mCherry knock-in reporter line, to generate and purify human pluripotent stem cell-derived SAN cells (hPSC-SAN), displaying molecular and electrophysiological characteristics of bona-fide nodal cells. We modeled cell type specific toxicity upon treatment with doxorubicin (DOXO) using hPSC-SAN generated from a library of induced pluripotent stem cells (iPSCs). We discovered 3 new genetic loci associated with increased sensitivity to DOXO-induced hPSC-SAN death. Genetic variants in these loci were associated with significantly higher early arrhythmia risk in patients receiving DOXO, confirmed by an unbiased PheWAS analysis. Finally, the in vitro DOXO assay enabled an unbiased drug screening platform and identification of physcion as a candidate therapeutic that can partially block DOXO-mediated cardiac toxicity.

2021-07-01 | GSE118085 | GEO

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [SNP array]

2021-07-01 | GSE118086 | GEO

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells

Project description:Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells

| PRJNA484391 | ENA

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [SNP array]

Project description:Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [SNP array]

| PRJNA484393 | ENA

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [RNA-seq]

Project description:Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [RNA-seq]

| PRJNA484392 | ENA

Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [scRNA-Seq]

Project description:Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [scRNA-Seq]

| PRJNA489896 | ENA

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery.

Project description:Anticancer chemotherapies have been shown to produce severe side effects, with cardiotoxicity from anthracycline being the most notable. Identifying risk factors for anticancer therapy-induced cardiotoxicity in cancer patients as well as understanding its underlying mechanism is essential to improving clinical outcomes of chemotherapy treatment regimens. Moreover, cardioprotective agents against anticancer therapy-induced cardiotoxicity are scarce. Human induced pluripotent stem cell technology offers an attractive platform for validation of potential single nucleotide polymorphism with increased risk for cardiotoxicity. Successful validation of risk factors and mechanism of cardiotoxicity would aid the development of such platform for novel drug discovery and facilitate the practice of personalized medicine.

| S-EPMC8090862 | biostudies-literature

Anthracycline-Induced Cardiotoxicity: Molecular Insights Obtained from Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs).

Project description:Anthracyclines are a class of chemotherapy drugs that are highly effective for the treatment of human cancers, but their clinical use is limited by associated dose-dependent cardiotoxicity. The precise mechanisms by which individual anthracycline induces cardiotoxicity are not fully understood. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are emerging as a physiologically relevant model to assess drugs cardiotoxicity. Here, we describe an assay platform by coupling hiPSC-CMs and impedance measurement, which allows real-time monitoring of cardiomyocyte cellular index, beating amplitude, and beating rate. Using this approach, we have performed comparative studies on a panel of four anthracycline drugs (doxorubicin, epirubicin, idarubicin, and daunorubicin) which share a high degree of structural similarity but are associated with distinct cardiotoxicity profiles and maximum cumulative dose limits. Notably, results from our hiPSC-CMs impedance model (dose-dependent responses and EC50 values) agree well with the recommended clinical dose limits for these drugs. Using time-lapse imaging and RNAseq, we found that the differences in anthracycline cardiotoxicity are closely linked to extent of cardiomyocyte uptake and magnitude of activation/inhibition of several cellular pathways such as death receptor signaling, ROS production, and dysregulation of calcium signaling. The results provide molecular insights into anthracycline cardiac interactions and offer a novel assay system to more robustly assess potential cardiotoxicity during drug development.

| S-EPMC7956936 | biostudies-literature

Induced Pluripotent HD Monkey Stem Cells Derived Neural Cells for Drug Discovery.

Project description:Huntington's disease (HD) is a neurodegenerative disease caused by an expansion of CAG trinucleotide repeat (polyglutamine [polyQ]) in the huntingtin ( HTT) gene, which leads to the formation of mutant HTT (mHTT) protein aggregates. In the nervous system, an accumulation of mHTT protein results in glutamate-mediated excitotoxicity, proteosome instability, and apoptosis. Although HD pathogenesis has been extensively studied, effective treatment of HD has yet to be developed. Therapeutic discovery research in HD has been reported using yeast, cells derived from transgenic animal models and HD patients, and induced pluripotent stem cells from patients. A transgenic nonhuman primate model of HD (HD monkey) shows neuropathological, behavioral, and molecular changes similar to an HD patient. In addition, neural progenitor cells (NPCs) derived from HD monkeys can be maintained in culture and differentiated to neural cells with distinct HD cellular phenotypes including the formation of mHTT aggregates, intranuclear inclusions, and increased susceptibility to oxidative stress. Here, we evaluated the potential application of HD monkey NPCs and neural cells as an in vitro model for HD drug discovery research.

| S-EPMC5699456 | biostudies-literature

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