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| Status |
Public on Jul 05, 2019 |
| Title |
Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
RNA-seq of iPSC-CMs.
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| Contributor(s) |
Lee J, Termglinchan V, Ioannis K, Wu JC |
| Citation(s) |
31316208 |
| |
| Submission date |
Aug 21, 2018 |
| Last update date |
Aug 15, 2019 |
| Contact name |
Lei Tian |
| E-mail(s) |
[email protected]
|
| Phone |
6502388262
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| Organization name |
Stanford's Postdoctoral Scholar programs
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| Street address |
1215 Welch Rd
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE118885 |
Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy |
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| Relations |
| BioProject |
PRJNA487109 |
| SRA |
SRP158544 |
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