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

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE119682 | GEO | 2021/07/01

REPOSITORIES: GEO

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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:This SuperSeries is composed of the SubSeries listed below.

2021-07-01 | GSE118087 | GEO

RNA-sequencing of Shox2 knockout and wildtype mouse embryonic stem cell-derived sinoatrial node-like cardiomyocytes

Project description:Differential RNA-seq-based expression profiling of Shox2+/+ and Shox2-/- ESC-derived sinoatrial node-like cardiomyocytes

2021-03-26 | GSE165544 | 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 [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

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 [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

SARS-CoV-2 Infection Induces Ferroptosis of Human Pluripotent Stem Cell-Derived Sinoatrial Nodal like Pacemaker Cells [single-cell RNA-seq]

Project description:We established an efficient strategy to derive functional human SAN like pacemaker cells for disease modeling and drug screening. We used a dual-reporter cell line(SHOX2-GFP+MYH6-mcherry) to indicate the sinoatrial nodal like pacemaker cells. We sorted out the double positive cell population after Day20 and prepared the sample for single cell RNA seq analysis.

2022-01-26 | GSE193723 | GEO

Mouse sinoatrial node transcriptome

Project description:RNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells Rationale: Treatment of sinus node disease with regenerative or cell-based therapies will require a detailed understanding of gene regulatory networks in cardiac pacemaker cells (PCs). Objective: To characterize the transcriptome of PCs using RNA sequencing, and to identify transcriptional networks responsible for PC gene expression. Methods and Results: We used laser capture micro-dissection (LCM) on a sinus node reporter mouse line to isolate RNA from PCs for RNA sequencing (RNA-Seq). Differential expression and network analysis identified novel SAN-enriched genes, and predicted that the transcription factor Islet-1 (Isl1) is active in developing pacemaker cells. RNA-Seq on SAN tissue lacking Isl1 established that Isl1 is an important transcriptional regulator within the developing SAN. Conclusions: (1) The PC transcriptome diverges sharply from other cardiomyocytes; (2) Isl1 is a positive transcriptional regulator of the PC gene expression program. There are 25 RNA-Sequencing Samples

2015-02-06 | E-GEOD-65658 | biostudies-arrayexpress

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