Genome-wide analysis of alternative splicing during human heart development

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作者
He Wang
Yanmei Chen
Xinzhong Li
Guojun Chen
Lintao Zhong
Gangbing Chen
Yulin Liao
Wangjun Liao
Jianping Bin
机构
[1] State Key Laboratory of Organ Failure Research,Department of Cardiology
[2] Nanfang Hospital,Department of Cardiology
[3] Southern Medical University,Department of Oncology
[4] Second Affiliated Hospital of Nanchang University,undefined
[5] Nanfang Hospital,undefined
[6] Southern Medical University,undefined
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Scientific Reports | / 6卷
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摘要
Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.
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