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Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes

BACKGROUND: 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...

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Autores principales: Lei, Wei, Feng, Tingting, Fang, Xing, Yu, You, Yang, Junjie, Zhao, Zhen-Ao, Liu, Junwei, Shen, Zhenya, Deng, Wenbo, Hu, Shijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845222/
https://www.ncbi.nlm.nih.gov/pubmed/29523209
http://dx.doi.org/10.1186/s13287-018-0793-5
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author Lei, Wei
Feng, Tingting
Fang, Xing
Yu, You
Yang, Junjie
Zhao, Zhen-Ao
Liu, Junwei
Shen, Zhenya
Deng, Wenbo
Hu, Shijun
author_facet Lei, Wei
Feng, Tingting
Fang, Xing
Yu, You
Yang, Junjie
Zhao, Zhen-Ao
Liu, Junwei
Shen, Zhenya
Deng, Wenbo
Hu, Shijun
author_sort Lei, Wei
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: 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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spelling pubmed-58452222018-03-19 Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes Lei, Wei Feng, Tingting Fang, Xing Yu, You Yang, Junjie Zhao, Zhen-Ao Liu, Junwei Shen, Zhenya Deng, Wenbo Hu, Shijun Stem Cell Res Ther Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-0793-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-09 /pmc/articles/PMC5845222/ /pubmed/29523209 http://dx.doi.org/10.1186/s13287-018-0793-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lei, Wei
Feng, Tingting
Fang, Xing
Yu, You
Yang, Junjie
Zhao, Zhen-Ao
Liu, Junwei
Shen, Zhenya
Deng, Wenbo
Hu, Shijun
Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes
title Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes
title_full Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes
title_fullStr Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes
title_full_unstemmed Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes
title_short Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes
title_sort signature of circular rnas in human induced pluripotent stem cells and derived cardiomyocytes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845222/
https://www.ncbi.nlm.nih.gov/pubmed/29523209
http://dx.doi.org/10.1186/s13287-018-0793-5
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