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Series GSE185689 Query DataSets for GSE185689
Status Public on Dec 01, 2021
Title miRNA-seq in healthy human iPSC-derived cardiomyocytes
Organism Homo sapiens
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Abnormalities of ventricular action potential (AP) cause malignant cardiac arrhythmias and sudden cardiac death. Here, we sought to identify microRNAs (miRNAs) that regulate the human cardiac AP and asked whether their manipulation allows for therapeutic modulation of AP abnormalities. Quantitative analysis of the miRNA targetomes in human cardiac myocytes identified miR-365 as a primary miRNA to regulate repolarizing ion channels. AP recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs) showed that elevation of miR-365 level significantly prolonged AP duration in hiPSC-CMs derived from a Short-QT syndrome (SQTS) patient, whereas specific inhibition of miR-365 normalized pathologically prolonged AP in Long-QT syndrome (LQTS) iPSC-CMs. Transcriptome analyses in human iPSC-CMs at bulk and single-cell level corroborated the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional AP-regulating genes by this miRNA. Whole-cell patch clamp experiments revealed miR-365-based regulation of repolarizing ionic currents. Finally, refractory period measurements in human myocardial slices substantiated the prolonging effect of miR-365 on AP duration also in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac AP duration by targeting key factors of cardiac repolarization.
 
Overall design small RNA-seq of 2 healthy hiPSC-CMs at day 60
 
Contributor(s) Esfandyari D, Engelhardt S
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Submission date Oct 11, 2021
Last update date Dec 02, 2021
Contact name Dena Esfandyari
E-mail(s) dena.esfandyari@tum.de, dena.esf@gmail.com
Phone 08941403286
Organization name Technical University of Munich
Department Institute of Pharmacology and Toxicology
Street address Haus 607, Biedersteiner Str. 29, IPT
City Munich
State/province Bavaria
ZIP/Postal code 80802
Country Germany
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (2)
GSM5621623 healthy_hiPSCCM_1 [miRNA-seq]
GSM5621624 healthy_hiPSCCM_2 [miRNA-seq]
This SubSeries is part of SuperSeries:
GSE185690 The regulatory role of miR-365 in human iPSC-derived cardiac myocytes
Relations
BioProject PRJNA770439
SRA SRP340888

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE185689_RAW.tar 50.0 Kb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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