Electrophysiologic Characterization of Calcium Handling in Human Induced Pluripotent Stem Cell-Derived Atrial Cardiomyocytes

被引：45

作者：

Argenziano, Mariana ^{[1
,2
]}

Lambers, Erin ^{[1
]}

Hong, Liang ^{[1
]}

Sridhar, Arvind ^{[1
]}

Zhang, Meihong ^{[1
]}

Chalazan, Brandon ^{[1
]}

Menon, Ambili ^{[1
]}

Savio-Galimberti, Eleonora ^{[1
,2
]}

Wu, Joseph C. ^{[3
]}

Rehman, Jalees ^{[1
,4
]}

Darbar, Dawood ^{[1
,4
]}

机构：

[1] Univ Illinois, Div Cardiol, Dept Med, 840 S Wood St,920S MC 715, Chicago, IL 60612 USA

[2] Lankenau Inst Med Res, Wynnewood, PA USA

[3] Stanford Univ, Med Ctr, Dept Med, Div Cardiol,Stanford Cardiovasc Inst, Stanford, CA 94305 USA

[4] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA

来源：

STEM CELL REPORTS | 2018年 / 10卷 / 06期

关键词：

COUP-TFII; FIBRILLATION; CHANNEL; DIFFERENTIATION;

D O I：

10.1016/j.stemcr.2018.04.005

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes (CMs) hold great promise for elucidating underlying cellular mechanisms that cause atrial fibrillation (AF). In order to use atrial-like hiPSC-CMs for arrhythmia modeling, it is essential to better understand the molecular and electrophysiological phenotype of these cells. We performed comprehensive molecular, transcriptomic, and electrophysiologic analyses of retinoic acid (RA)-guided hiPSC atrial-like CMs and demonstrate that RA results in differential expression of genes involved in calcium ion homeostasis that directly interact with an RA receptor, chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TFII). We report a mechanism by which RA generates an atrial-like electrophysiologic signature through the downstream regulation of calcium channel gene expression by COUP-TFII and modulation of calcium handling. Collectively, our results provide important insights into the underlying molecular mechanisms that regulate atrial-like hiPSC-CM electrophysiology and support the use of atrial-like CMs derived from hiPSCs to model AF.

引用

页码：1867 / 1878

页数：12

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