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Series GSE118883 Query DataSets for GSE118883
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
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.
 
Overall design ATAC-seq of iPSC-CMs.
 
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) tianlei@stanford.edu
Phone 6502388262
Organization name Stanford's Postdoctoral Scholar programs
Street address 1215 Welch Rd
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
 
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (4)
GSM3349778 ATAC-seq_III-3-WT, rep1
GSM3349779 ATAC-seq_III-3-WT, rep2
GSM3349780 ATAC-seq_III-3-MT, rep1
This SubSeries is part of SuperSeries:
GSE118885 Dysregulation of PDGFRB contributes to the pathogenesis of LMNA-related dilated cardiomyopathy
Relations
BioProject PRJNA487112
SRA SRP158545

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Supplementary file Size Download File type/resource
GSE118883_PT3MT_ATAC_USPD16084652_HJ35WBBXX_L8_1.trim.PE2SE.nodup.tn5_pooled.pf.fc.signal.bigwig 899.8 Mb (ftp)(http) BIGWIG
GSE118883_PT3WT_ATAC_USPD16084651_HJ35WBBXX_L8_1.trim.PE2SE.nodup.tn5_pooled.pf.fc.signal.bigwig 588.7 Mb (ftp)(http) BIGWIG
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Raw data are available in SRA
Processed data are available on Series record

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