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Series GSE106506 Query DataSets for GSE106506
Status Public on Dec 14, 2018
Title Differential Wnt-mediated Programming and Arrhythmogenesis in Right versus Left Ventricles [wntgof]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Several inherited arrhythmias primarily affect the right ventricle, including Brugada syndrome and arrhythmogenic cardiomyopathy, however the molecular basis of this chamber predilection is not well understood. Right and left ventricular cardiomyocytes derive from distinct progenitor populations. Here, we show that Hrt2, a gene associated with Brugada syndrome, is a direct target of Wnt signaling in the right ventricle and Notch signaling in the left ventricle. Perturbations of Wnt and Notch signaling during development and in the adult lead to chamber-specific transcriptional effects on Hrt2 expression associated with distinct binding patterns to Hrt2 enhancers. Differential enhancer binding is present at early developmental stages when the signaling pathways are active and persists into adulthood. Consistent with chamber-specific regulation, mice deficient in Wnt transcriptional activity dysregulate only a small fraction of transcripts in common between ventricles. Wnt target gen es important for cellular electrophysiology are differentially regulated, resulting in perturbed cardiac conduction and cellular electrophysiological parameters only within the right ventricle. Ex vivo and in vivo physiologic stimulation of the right ventricle is sufficient to induce ventricular tachycardia in Wnt transcriptionally inactive hearts, while left ventricular stimulation has no effect. Taken together, these data delineate mechanisms underlying ventricular-specific arrhythmia susceptibility due to embryonic programming.
Overall design RNA-seq data of Wnt GOF ventricles from e12.5 embryonic hearts
n=6 for each group (control ventricles, wntgof ventricles)
Contributor(s) Khandekar A, Li RG, Rentschler S
Citation(s) 30193957
Submission date Nov 03, 2017
Last update date May 15, 2019
Contact name Bo Zhang
Phone 3143624757
Organization name Washington University School of Medicine
Department Developmental Biology
Lab Zhang
Street address 4515 McKinley Research Bldg 03212
City Saint Louis
State/province Missouri
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM2839388 1c (wntgof)
GSM2839389 2c (wntgof)
GSM2839390 3c (wntgof)
This SubSeries is part of SuperSeries:
GSE106509 Differential Wnt-mediated Programming and Arrhythmogenesis in Right versus Left Ventricles
BioProject PRJNA417134
SRA SRP123761

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE106506_WntGOF_DE.txt.gz 2.6 Mb (ftp)(http) TXT
GSE106506_all.gene_counts.txt.gz 1.5 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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