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Status |
Public on Jul 05, 2019 |
Title |
Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy [ATAC-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy 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 |
ATAC-seq of iPSC-CMs.
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Contributor(s) |
Lee J, Termglinchan V, Ioannis K, Wu JC |
Citation(s) |
31316208 |
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Submission date |
Aug 21, 2018 |
Last update date |
Aug 15, 2019 |
Contact name |
Lei Tian |
E-mail(s) |
tianlei@stanford.edu
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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 (4)
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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 |
PRJNA487112 |
SRA |
SRP158545 |