@article{9addb7ab921d41a1aefa6ded9db1e784,
title = "iPSC-derived cardiomyocytes reveal abnormal TGF-β signalling in left ventricular non-compaction cardiomyopathy",
abstract = "Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and this was associated with perturbed transforming growth factor beta (TGF-β) signalling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGF-β signalling. TBX20 regulates the expression of TGF-β signalling modifiers including one known to be a genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGF-β signalling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC.",
author = "Kazuki Kodo and Ong, {Sang Ging} and Fereshteh Jahanbani and Vittavat Termglinchan and Keiichi Hirono and Kolsoum Inanloorahatloo and Ebert, {Antje D.} and Praveen Shukla and Abilez, {Oscar J.} and Churko, {Jared M.} and Ioannis Karakikes and Gwanghyun Jung and Fukiko Ichida and Wu, {Sean M.} and Snyder, {Michael P.} and Daniel Bernstein and Wu, {Joseph C.}",
note = "Funding Information: We are grateful for the support provided by the Neuroscience Microscopy Service (NMS), and FACS Core at the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University. This work is supported by the Uehara Memorial Foundation Research Fellowship, American Heart Association Postdoctoral Fellowship 15POST25160016 (K.K.), American Heart Association Postdoctoral Fellowship 15POST22940013 and NIH K99HL130416 (S.-G.O.), The Ministry of Education, Culture, Sports, Science and Technology in Japan (F.I.), National Institutes of Health P01 GM099130 (M.P.S.), NIH K18 HL11708301, Children's Cardiomyopathy Foundation (D.B.), AHA Established Investigator Award, NIH R01 HL113006, NIH R01 HL130020, NIH R01 126527, NIH R01 128170, NIH R01 HL123968 and NIH R24 HL117756 (J.C.W.). Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited, part of Springer Nature.",
year = "2016",
month = sep,
day = "28",
doi = "10.1038/ncb3411",
language = "English",
volume = "18",
pages = "1031--1042",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "10",
}