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Title: Phenotype-Based High-Throughput Classification of Long QT Syndrome Subtypes Using Human Induced Pluripotent Stem Cells
Authors: Yoshinaga, Daisuke
Baba, Shiro
Makiyama, Takeru
Shibata, Hirofumi
Hirata, Takuya
Akagi, Kentaro
Matsuda, Koichi
Kohjitani, Hirohiko
Wuriyanghai, Yimin
Umeda, Katsutsugu
Yamamoto, Yuta
Conklin, Bruce R.
Horie, Minoru
Takita, Junko
Heike, Toshio
Author's alias: 吉永, 大介
馬場, 志郎
牧山, 武
柴田, 洋史
赤木, 健太郎
松田, 浩一
糀谷, 泰彦
梅田, 雄嗣
滝田, 順子
平家, 俊男
Keywords: long QT syndrome
induced pluripotent stem cell
phenotype-based diagnosis
multi-electrode array
genome editing
Issue Date: 13-Aug-2019
Publisher: Elsevier BV
Journal title: Stem cell reports
Volume: 13
Issue: 2
Start page: 394
End page: 404
Abstract: For long QT syndrome (LQTS), recent progress in genome-sequencing technologies enabled the identification of rare genomic variants with diagnostic, prognostic, and therapeutic implications. However, pathogenic stratification of the identified variants remains challenging, especially in variants of uncertain significance. This study aimed to propose a phenotypic cell-based diagnostic assay for identifying LQTS to recognize pathogenic variants in a high-throughput manner suitable for screening. We investigated the response of LQT2-induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) following IKr blockade using a multi-electrode array, finding that the response to IKr blockade was significantly smaller than in Control-iPSC-CMs. Furthermore, we found that LQT1-iPSC-CMs and LQT3-iPSC-CMs could be distinguished from Control-iPSC-CMs by IKs blockade and INa blockade, respectively. This strategy might be helpful in compensating for the shortcomings of genetic testing of LQTS patients.
Rights: © 2019 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
URI: http://hdl.handle.net/2433/245674
DOI(Published Version): 10.1016/j.stemcr.2019.06.007
PubMed ID: 31378668
Appears in Collections:Journal Articles

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