RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model.
RNA expression profiling of human iPSC-derived cardiomyocytes in a cardiac hypertrophy model.
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DOI：
10.1371/journal.pone.0108051
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Broeckel U
中科院分区：
文献类型：
--
作者：
Aggarwal P;Turner A;Matter A;Kattman SJ;Stoddard A;Lorier R;Swanson BJ;Arnett DK;Broeckel U
心肌肥厚是心血管疾病和心力衰竭的独立危险因素。越来越多的证据表明，microRNAs（miRNAs）在信使RNA（mRNA）的调控和各种心血管疾病的发病机制中发挥着重要作用。然而，在基因调控水平上全面研究心脏肥大的能力受到人类心肌细胞有限可用性的影响。人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）为疾病建模提供了机会。在这里，我们利用先前建立的体外模型的心脏肥大，询问与心脏疾病的过程相关的调节机制。我们对内皮素1（ET-1）刺激的hiPSC-CM进行miRNA测序和mRNA表达分析，以描述相关的RNA表达谱。MicroRNA测序显示，ET-1刺激和未刺激的对照hiPSC-CM之间有超过250种已知和34种预测的新型miRNA差异表达。信使RNA表达分析鉴定了731个具有显著差异表达的探针组。对显著差异表达的miRNAs和mRNAs的计算靶标预测鉴定了近2000个靶标对。比较体外数据与人心肌活检的主成分分析方法检测到体外样品与左心室肥厚心肌活检之间的重叠表达变化。这些结果提供了进一步的见解复杂的RNA调控机制与心脏肥大。
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.
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DOI：
10.1291/hypres.22.1
发表时间：
1999-03-01
期刊：
HYPERTENSION RESEARCH-CLINICAL AND EXPERIMENTAL
影响因子：
--
作者：
Devereux, RB;Roman, MJ
通讯作者：
Roman, MJ
影响因子：
14.9
作者：
Dai X;Zhao PX
通讯作者：
Zhao PX
影响因子：
3.7
作者：
Bupha-Intr T;Haizlip KM;Janssen PM
通讯作者：
Janssen PM
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S