Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes.
Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes.
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人诱导多能干细胞和衍生心肌细胞中环状 RNA 的特征
DOI：
10.1186/s13287-018-0793-5
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发表时间：
2018-03-09
影响因子：
7.5
通讯作者：
Hu S
中科院分区：
文献类型：
--
作者：
Lei W;Feng T;Fang X;Yu Y;Yang J;Zhao ZA;Liu J;Shen Z;Deng W;Hu S
环状RNA（CircRNA）是一类新型的非编码RNA调节子。虽然通过对RNA-seq数据的生物信息学分析已经鉴定出了一些circRNA，但组织和疾病特异性circRNA仍有待发现，以促进其在基础研究和临床实践中的应用。本研究的目的是探索人类诱导多能干细胞（hiPSC）和hiPSC衍生的心肌细胞（hiPSC-CM）中的circRNA谱，并鉴定心脏或疾病特异性circRNA。hiPSC由成纤维细胞产生，然后通过在RPMI+B27培养基中调节WNT信号传导进一步分化为hiPSC-CM。在高通量RNA测序后，通过称为CIRCexplorer的组合策略提取并定量circRNA。进行整合分析以阐明circRNA与其亲本线性异构体之间的相关性。通过定量逆转录PCR证实了circRNA的心脏和疾病特异性表达。在这项研究中，在hiPSC和hiPSC-CM中鉴定了总共5602个circRNA。我们的数据首次表明，与未分化的hiPSC相比，分化的心肌细胞中circRNA的表达更丰富。除了宿主基因依赖性表达外，我们的综合分析还鉴定了许多在hiPSC和hiPSC-CM中显示宿主基因非依赖性表达的circRNA。circRNA包括circSLC 8A 1、circCACNA 1D、circSPHKAP和circALPK 2在心脏分化过程中显示心脏选择性表达，并在胎儿组织中显示人类心脏特异性富集。此外，扩张型心肌病患者的心脏组织中circSLC 8A 1异常增加。circRNA在hiPSC分化的CM中高度富集，并且心脏特异性circRNA如circSLC 8A 1、circCACNA 1D、circSPHKAP和circALPK 2可作为CM的生物标志物。检测circSLC 8A 1的过度表达为心脏病的病理状态指示提供了潜在的方法。本文的在线版本（10.1186/s13287-018-0793-5）包含补充材料，可供授权用户使用。
Circular RNAs (circRNAs) are regarded as a novel class of noncoding RNA regulators. Although a number of circRNAs have been identified by bioinformatics analysis of RNA-seq data, tissue and disease-specific circRNAs are still to be uncovered to promote their application in basic research and clinical practice. The purpose of this study was to explore the circRNA profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived cardiomyocytes (hiPSC-CMs), and to identify cardiac or disease-specific circRNAs. hiPSCs were generated from fibroblasts, and then further differentiated to hiPSC-CMs by modulating WNT signaling in RPMI+B27 medium. Following high-throughput RNA sequencing, circRNAs were extracted and quantified by a combined strategy known as CIRCexplorer. Integrative analysis was performed to illuminate the correlation between circRNAs and their parental linear isoforms. Cardiac and disease-specific expression of circRNAs was confirmed by quantitative reverse-transcription PCR. In this study, a total of 5602 circRNAs were identified in hiPSCs and hiPSC-CMs. Our data indicated, for the first time, more enriched expression of circRNAs in differentiated cardiomyocytes than in undifferentiated hiPSCs. In addition to the host gene-dependent expression, our integrative analysis also identified a number of circRNAs showing host gene-independent expression in hiPSCs and hiPSC-CMs. CircRNAs including circSLC8A1, circCACNA1D, circSPHKAP and circALPK2 showed cardiac-selective expression during cardiac differentiation and human heart-specific enrichment in fetal tissues. Furthermore, circSLC8A1 abnormally increased in heart tissues from patients suffering from dilated cardiomyopathy. CircRNAs are highly enriched in hiPSC-differentiated CMs, and cardiac-specific circRNAs such as circSLC8A1, circCACNA1D, circSPHKAP and circALPK2 may serve as biomarkers of CMs. Detection of the excessive expression of circSLC8A1 provides a potential approach for pathological status indication of heart disease. The online version of this article (10.1186/s13287-018-0793-5) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
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通讯作者：
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影响因子：
64.8
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Laflamme, Michael A.
影响因子：
4.6
作者：
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通讯作者：
Pils D
影响因子：
5.2
作者：
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通讯作者：
Wu, Joseph C.
circRNADb：具有蛋白质编码注释的人类环状 RNA 综合数据库
影响因子：
4.6
作者：
Chen X;Han P;Zhou T;Guo X;Song X;Li Y
通讯作者：
Li Y