[PDF][PDF] Electrophysiologic characterization of calcium handling in human induced pluripotent stem cell-derived atrial cardiomyocytes

M Argenziano, E Lambers, L Hong, A Sridhar, M Zhang… - Stem cell reports, 2018 - cell.com
M Argenziano, E Lambers, L Hong, A Sridhar, M Zhang, B Chalazan, A Menon…
Stem cell reports, 2018cell.com
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 …
Summary
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.
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