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Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients

Congenital heart disease (CHD) is the most serious congenital defect in newborns with higher mortality. Alternative splicing (AS) plays an essential role in numerous heart diseases. However, our understanding of the link between mRNA splicing and CHD in humans is limited. Here, we try to investigate...

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Autores principales: Xu, Xiang, Zou, Renchao, Liu, Xiaoyong, Su, Qianqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388029/
https://www.ncbi.nlm.nih.gov/pubmed/35984151
http://dx.doi.org/10.1097/MD.0000000000030123
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author Xu, Xiang
Zou, Renchao
Liu, Xiaoyong
Su, Qianqian
author_facet Xu, Xiang
Zou, Renchao
Liu, Xiaoyong
Su, Qianqian
author_sort Xu, Xiang
collection PubMed
description Congenital heart disease (CHD) is the most serious congenital defect in newborns with higher mortality. Alternative splicing (AS) plays an essential role in numerous heart diseases. However, our understanding of the link between mRNA splicing and CHD in humans is limited. Here, we try to investigate the genome-wide AS events in CHD using bioinformatics methods. We collected available RNA-seq datasets of CHD-induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) (including single ventricle disease [SVD] and tetralogy of Fallot [TOF]) and non-CHD from the Gene Expression Omnibus database. Then, we unprecedentedly performed AS profiles in CHD-iPSC-CMs and non-CHD-iPSC-CMs. The rMAPS was used to generate RNA-maps for the analysis of RNA-binding proteins’ (RBPs) binding sites. We used StringTie to identify and quantify the transcripts from aligned RNA-Seq reads. A quantification matrix was generated with respect to different groups by extracting the transcripts per million values from StringTie outputs. Then, this matrix was used for correlation analysis between the expression level of RBP and AS level. Finally, we validated our AS results using RNA-seq data from CHD and non-CHD patient tissue samples. We identified CHD-related AS events using CHD-iPSC-CMs and CHD samples from patients. The results showed that functional enrichment of abnormal AS in SVD and TOF was transcription factor-related. Using rMAPS, RNA-binding proteins which regulated these AS were also determined, and RBP-AS regulatory network was constructed. Overall, we identified abnormal AS in CHD-iPSC-CMs and CHD samples from patients. We predicted AS regulators in SVD and TOF, respectively. At last, we concluded that AS played a key role in the pathogenesis of CHD.
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spelling pubmed-93880292022-08-23 Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients Xu, Xiang Zou, Renchao Liu, Xiaoyong Su, Qianqian Medicine (Baltimore) Research Article Congenital heart disease (CHD) is the most serious congenital defect in newborns with higher mortality. Alternative splicing (AS) plays an essential role in numerous heart diseases. However, our understanding of the link between mRNA splicing and CHD in humans is limited. Here, we try to investigate the genome-wide AS events in CHD using bioinformatics methods. We collected available RNA-seq datasets of CHD-induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) (including single ventricle disease [SVD] and tetralogy of Fallot [TOF]) and non-CHD from the Gene Expression Omnibus database. Then, we unprecedentedly performed AS profiles in CHD-iPSC-CMs and non-CHD-iPSC-CMs. The rMAPS was used to generate RNA-maps for the analysis of RNA-binding proteins’ (RBPs) binding sites. We used StringTie to identify and quantify the transcripts from aligned RNA-Seq reads. A quantification matrix was generated with respect to different groups by extracting the transcripts per million values from StringTie outputs. Then, this matrix was used for correlation analysis between the expression level of RBP and AS level. Finally, we validated our AS results using RNA-seq data from CHD and non-CHD patient tissue samples. We identified CHD-related AS events using CHD-iPSC-CMs and CHD samples from patients. The results showed that functional enrichment of abnormal AS in SVD and TOF was transcription factor-related. Using rMAPS, RNA-binding proteins which regulated these AS were also determined, and RBP-AS regulatory network was constructed. Overall, we identified abnormal AS in CHD-iPSC-CMs and CHD samples from patients. We predicted AS regulators in SVD and TOF, respectively. At last, we concluded that AS played a key role in the pathogenesis of CHD. Lippincott Williams & Wilkins 2022-08-19 /pmc/articles/PMC9388029/ /pubmed/35984151 http://dx.doi.org/10.1097/MD.0000000000030123 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
spellingShingle Research Article
Xu, Xiang
Zou, Renchao
Liu, Xiaoyong
Su, Qianqian
Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
title Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
title_full Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
title_fullStr Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
title_full_unstemmed Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
title_short Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
title_sort alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388029/
https://www.ncbi.nlm.nih.gov/pubmed/35984151
http://dx.doi.org/10.1097/MD.0000000000030123
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