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Series GSE63161 Query DataSets for GSE63161
Status Public on Jul 13, 2016
Title hiPSCs unravel aberrant TGFβ signaling as an etiology of left ventricular non-compaction
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and has a unique phenotype with characteristically extensive hypertrabeculation of the left ventricle, similar to the embryonic left ventricle, suggesting a developmental defect of the embryonic myocardium. However, studying this disease has been challenging due to the lack of an animal model that can faithfully recapitulate the clinical phenotype of LVNC. To address this, we show that patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) generated from a family with LVNC recapitulated a developmental defect consistent with the LVNC phenotype at the single-cell level. We then utilized hiPSC-CMs to show that increased transforming growth factor beta (TGFβ) signaling is one of the central mechanisms underlying the pathogenesis of LVNC. LVNC hiPSC-CMs demonstrated decreased proliferative capacity due to abnormal activation of TGFβ signaling. Exome sequencing demonstrated a mutation in TBX20, which regulates TGFβ signaling, contributing to the LVNC phenotype. Our results demonstrate that hiPSC-CMs are a useful tool for the exploration of novel mechanisms underlying poorly understood cardiomyopathies such as LVNC. Here we provide the first evidence of activation of TGF signaling as playing a role in the pathogenesis of LVNC.
Overall design mRNA expression profiles in human iPSC derived cardiomyocytes obtained from 2 independent unrelated control, 1 asymptomatic mild DCM (2 iPSC lines) and 3 LVNC patients (2 proband lines and 1 lines from 2 siblings) 2 weeks after starting cardiac differentiation.
Contributor(s) Kodo K, Hu S, InanlooRahatloo K, Bernstein D, Wu JC
Citation(s) 27642787
Submission date Nov 10, 2014
Last update date May 15, 2019
Contact name Kazuki Kodo
Organization name Stanford
Street address campus street
City stanford
ZIP/Postal code 94305
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (8)
GSM1542461 control hiPSC-CMs at 2 weeks #1
GSM1542462 control hiPSC-CMs at 2 weeks #2
GSM1542463 mild DCM hiPSC-CMs at 2 weeks #1
BioProject PRJNA266836
SRA SRP049676

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

Supplementary file Size Download File type/resource
GSE63161_FPKM-all-samples.txt.gz 865.8 Kb (ftp)(http) TXT
GSE63161_diff-Gene-list.txt.gz 3.1 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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