Journal Article

RNA Expression Profiling of Human iPSC-Derived Cardiomyocytes in a Cardiac Hypertrophy Model

Turner, Amy, Broeckel, Ulrich, Aggarwal, Praful, Kattman, Steven J., Arnett, Donna K., Swanson, Bradley J., Lorier, Rachel, Stoddard, Alexander, Matter, Andrea

2014

Overview

Cardiac hypertrophy is an independent risk factor for cardiovascular disease and heart failure. There is increasing evidence that microRNAs (miRNAs) play an important role in the regulation of messenger RNA (mRNA) and the pathogenesis of various cardiovascular diseases. However, the ability to comprehensively study cardiac hypertrophy on a gene regulatory level is impacted by the limited availability of human cardiomyocytes. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer the opportunity for disease modeling. Here we utilize a previously established in vitro model of cardiac hypertrophy to interrogate the regulatory mechanism associated with the cardiac disease process. We perform miRNA sequencing and mRNA expression analysis on endothelin 1 (ET-1) stimulated hiPSC-CMs to describe associated RNA expression profiles. MicroRNA sequencing revealed over 250 known and 34 predicted novel miRNAs to be differentially expressed between ET-1 stimulated and unstimulated control hiPSC-CMs. Messenger RNA expression analysis identified 731 probe sets with significant differential expression. Computational target prediction on significant differentially expressed miRNAs and mRNAs identified nearly 2000 target pairs. A principal component analysis approach comparing the in vitro data with human myocardial biopsies detected overlapping expression changes between the in vitro samples and myocardial biopsies with Left Ventricular Hypertrophy. These results provide further insights into the complex RNA regulatory mechanism associated with cardiac hypertrophy.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Arrays / Biology / Biology and Life Sciences / Cardiomegaly - pathology / Cardiomyocytes / Cardiovascular diseases / Change detection / Computer applications / Coronary artery disease / Drug dosages / Endothelin / Endothelin 1 / Gene expression / Gene Expression Profiling / Gene sequencing / Health risks / Heart / Heart cells / Heart diseases / Heart failure / Heart hypertrophy / Humans / Hypertrophy / Induced Pluripotent Stem Cells - cytology / Mathematical models / Medicine and Health Sciences / MicroRNA / MicroRNAs / MicroRNAs - genetics / miRNA / Myocytes, Cardiac - cytology / Myocytes, Cardiac - metabolism / Pathogenesis / Pediatrics / Peptides / Pluripotency / Predictions / Principal components analysis / Regulatory mechanisms (biology) / Ribonucleic acid / Risk factors / RNA / RNA, Messenger - genetics / RNA, Messenger - metabolism / Rodents / Sequence Analysis, RNA / Stem cells / Studies / Target recognition / Ventricle