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| 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.
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| 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.
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| 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 |
| E-mail(s) |
kkodo@stanford.edu
|
| Organization name |
Stanford
|
| Street address |
campus street
|
| City |
stanford |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA266836 |
| SRA |
SRP049676 |
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