title: RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model.
abstract: 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.
authors.affiliation: Department of Pediatrics, Children's Research Institute, and Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Praful
authors.initials: P
authors.lastname: Aggarwal
authors.affiliation: Department of Pediatrics, Children's Research Institute, and Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Turner
authors.affiliation: Department of Pediatrics, Children's Research Institute, and Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matter
authors.affiliation: Cellular Dynamics International Inc., Madison, Wisconsin, United States of America.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kattman
authors.affiliation: Department of Pediatrics, Children's Research Institute, and Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoddard
authors.affiliation: Department of Pediatrics, Children's Research Institute, and Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lorier
authors.affiliation: Cellular Dynamics International Inc., Madison, Wisconsin, United States of America.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Swanson
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.affiliation: Department of Pediatrics, Children's Research Institute, and Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
mesh_terms: D006332:Cardiomegaly / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger