Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Highly efficient and multiplexed transcriptome profiling of cardiotoxicity induced by tyrosine kinase inhibitors

ABSTRACT: Highly efficient and multiplexed transcriptome profiling of cardiotoxicity induced by tyrosine kinase inhibitors

PROVIDER: PRJNA915054 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22868424_1.fastq.gz	Fastqsanger.gz
	SRR22868424_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 2 of 2

Similar Datasets

Highly efficient and multiplexed transcriptome profiling of cardiotoxicity induced by tyrosine kinase inhibitors

Project description:Tyrosine kinase inhibitors (TKIs) are anti-cancer therapeutics used in long-term treatment. However, many of them cause cardiotoxicity with limited cure. We aim to define molecular mechanisms of cardiotoxicity that can be targeted for oncocardiology treatment. Eight TKIs with different levels of cardiotoxicity were selected and transcriptome responses of human cardiomyocytes to them at varying doses and times were profiled using a high throughput RNAseq technique. Transcriptome changes are classified into 7 clusters with mainly single-drug clusters. Drug-specific effects on the transcriptome dominate over dose-, time- or toxicity-dependent effects. Two clusters with three TKIs (afatinib, ponatinib and sorafenib) have the top enriched pathway as the endoplasmic reticulum stress. These TKIs cause an increase in reactive oxygen species, lipid peroxidation, or calcium, and induce biased endoplasmic reticulum stress on the PERK and the IRE1α pathway. Inhibiting either PERK or IRE1α blocks expression of cardiomyocyte injury and pro-inflammatory markers. Our data contain rich information about stress responses of human cardiomyocytes to specific TKIs, representing potential molecular mechanisms of cardiotoxicity. ER stress-induced inflammation is a promising therapeutic target to mitigate ponatinib- and sorafenib-induced cardiotoxicity

2023-05-12 | GSE221595 | GEO

Tyrosine Kinase Inhibitor Cardiotoxicity

Project description:Tyrosine Kinase Inhibitor Cardiotoxicity

| PRJNA352077 | ENA

High-Throughput Screening of Human Induced Pluripotent Stem Cell Cardiomyocytes Predicts Tyrosine Kinase Inhibitor Cardiotoxicity

Project description:High-Throughput Screening of Human Induced Pluripotent Stem Cell Cardiomyocytes Predicts Tyrosine Kinase Inhibitor Cardiotoxicity

2016-10-20 | GSE88944 | GEO

Total RNA profiles in response to four tyrosine kinase inhibitors in human induced pluripotent stem cell-derived cardiomyocytes

Project description:To define molecular markers of tyrosine kinase inhibitor-induced cardiotoxicity, we measured transcriptome changes in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with one of four tyrosine kinase inhibitors (Erlotinib, Lapatinib, Sorafenib, or Sunitinib) displaying a range of mild to severe cardiotoxicity or a vehicle-only control (DMSO). Gene expression changes were assessed at the cell population level using total RNA-seq, which measured levels of both mRNAs and non-coding RNAs. hiPSC-CMs used in this study were the Cor.4U cells purchased from Ncardia.

2019-03-23 | GSE114686 | GEO

Efficient and multiplexed somatic genome editing with Cas12a mice

Project description:Efficient and multiplexed somatic genome editing with Cas12a mice

| PRJNA1210636 | ENA

High-Throughput Screening of Tyrosine Kinase Inhibitor Cardiotoxicity using Human Induced Pluripotent Stem Cells

Project description:Tyrosine kinase inhibitors (TKIs), despite efficacy as anti-cancer therapies, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We have utilized patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen FDA-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a “cardiac safety index” to assess cardiotoxicities of existing TKIs. Many TKIs with a low cardiac safety index exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that VEGFR2/PDGFR-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. Using phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Activating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during co-treatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anti-cancer TKIs, correlating with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling.

2016-11-02 | GSE89410 | GEO

Total protein profiles of human induced pluripotent stem cell-derived cardiomyocytes in response to four tyrosine kinase inhibitors

Project description:Drug-induced cardiotoxicity is a widespread clinical issue affecting numerous drug classes and remains difficult to treat. One such drug class is Tyrosine Kinase Inhibitors (TKIs), which cause varying degrees of contraction-related cardiotoxicity usually after weeks of exposure. Understanding molecular mechanisms underlying both acute and chronic toxicity of TKIs could help identify new treatment opportunities. Here, we presented transcriptome responses to four TKIs (Sunitinib, Sorafenib, Lapatinib and Erlotinib) across 3 doses and 4 time points in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Gene expression evolved continually under drug treatment and revealed changes in several biological networks that were associated with cardiac metabolism and contraction. These changes were confirmed by proteomics and resulted in metabolic and structural remodeling of hiPSC-CMs. One of the metabolic remodeling was the increased aerobic glycolysis induced by Sorafenib, which is an adaptive response in preserving cell survival under Sorafenib treatment. Drug adaptation in cardiac cells may represent new targets for managing chronic forms of TKI-induced cardiotoxicity.

2019-05-16 | PXD012043 | Pride

Highly multiplexed single-cell quantitative PCR

Project description:Highly multiplexed single-cell quantitative PCR

| PRJNA398516 | ENA

Highly multiplexed spatial transcriptomics in bacteria

Project description:Highly multiplexed spatial transcriptomics in bacteria

| PRJNA1117432 | ENA

Highly multiplexed single-cell quantitative PCR

Project description:We present a microfluidic device for rapid gene expression profiling in single cells using multiplexed quantitative polymerase chain reaction (qPCR). This device integrates all processing steps, including cell isolation and lysis, complementary DNA synthesis, pre-amplification, sample splitting, and measurement in twenty separate qPCR reactions. Each of these steps is performed in parallel on up to 200 single cells per run. Experiments performed on dilutions of purified RNA establish assay linearity over a dynamic range of at least 104, a qPCR precision of 15 %, and detection sensitivity down to a single cDNA molecule. We demonstrate the application of our device for rapid profiling of microRNA expression in single cells. Measurements performed on a panel of twenty miRNA in two types of cells revealed clear cell-to-cell heterogeneity, with evidence of spontaneous differentiation manifest as distinct expression signatures. Highly multiplexed microfluidic RT-qPCR fills a gap in current capabilities for single-cell analysis, providing a rapid and cost-effective approach for profiling panels of marker genes, thereby complementing single-cell genomics methods that are best suited for global analysis and discovery. We expect this approach to enable new studies requiring fast, cost-effective, and precise measurements across hundreds of single cells.

2018-01-31 | GSE102734 | 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