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| Status |
Public on Jul 01, 2021 |
| Title |
Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells [SNP array] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
|
| Summary |
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.
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| Overall design |
Human induced pluripotent stem cells were derived from individuals and sequenced for SNPs information.
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| Contributor(s) |
Chen S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Aug 03, 2018 |
| Last update date |
Jul 02, 2021 |
| Contact name |
Shuibing Chen |
| E-mail(s) |
shuibing.chen@gmail.com
|
| Phone |
2127465431
|
| Organization name |
Weill Cornell Medical College
|
| Department |
Surgery
|
| Street address |
A 827B, 1300 York Ave
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6801 |
[GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array |
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| Samples (42)
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| This SubSeries is part of SuperSeries: |
| GSE118087 |
Pharmacogenetics and Drug Discovery for Anthracycline-Induced Cardiotoxicity Enabled by Sinoatrial Node-like Cells Derived from Human Pluripotent Stem Cells |
|
| Relations |
| BioProject |
PRJNA484393 |
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