RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model. PLoS One 2014;9(9):e108051
Date
09/26/2014Pubmed ID
25255322Pubmed Central ID
PMC4177883DOI
10.1371/journal.pone.0108051Scopus ID
2-s2.0-84907587769 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
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.
Author List
Aggarwal P, Turner A, Matter A, Kattman SJ, Stoddard A, Lorier R, Swanson BJ, Arnett DK, Broeckel UAuthors
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinAmy Turner Research Scientist I in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
CardiomegalyGene Expression Profiling
Humans
Induced Pluripotent Stem Cells
MicroRNAs
Myocytes, Cardiac
RNA, Messenger
Sequence Analysis, RNA
