• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人类心脏发育过程中可变剪接的全基因组分析。

Genome-wide analysis of alternative splicing during human heart development.

作者信息

Wang He, Chen Yanmei, Li Xinzhong, Chen Guojun, Zhong Lintao, Chen Gangbing, Liao Yulin, Liao Wangjun, Bin Jianping

机构信息

Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Department of Cardiology, Second Affiliated Hospital of Nanchang University, Jiangxi 330006, China.

出版信息

Sci Rep. 2016 Oct 18;6:35520. doi: 10.1038/srep35520.

DOI:10.1038/srep35520
PMID:27752099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5067579/
Abstract

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.

摘要

可变剪接（AS）在小鼠心脏发育过程中驱动决定性变化。近期高通量技术的进步推动了全基因组范围内的可变剪接研究，然而其在人类胎儿心脏向成人阶段转变过程中的分析尚未见报道。在此，我们展示了对人类胎儿和成人心脏之间可变剪接转变的高分辨率全局分析。RNA测序数据表明，人类胎儿和成人心脏之间发生了广泛的可变剪接转变，且可变剪接事件在蛋白质编码基因中比在长链非编码RNA（lncRNA）中更频繁发生。胎儿和成人心脏之间的可变剪接模式存在显著差异。使用人类心脏样本的定量逆转录-聚合酶链反应分析进一步证实了可变剪接事件的预测差异。功能性胎儿特异性可变剪接事件分析显示，其与包括细胞周期在内的细胞增殖相关途径富集有关，而成人特异性可变剪接事件则与蛋白质合成有关。此外，42.6%的胎儿特异性可变剪接事件在胎儿和成人心脏之间的基因表达水平上显示出显著变化。同时表现出胎儿特异性可变剪接和差异表达的基因在细胞周期相关功能中高度富集。总之，我们提供了胎儿和成人心脏之间可变剪接转变的全基因组概况，并提出可变剪接转变和差异基因表达可能在人类心脏发育中起决定性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/0ae5e1e5adb5/srep35520-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/6f1546e7b52d/srep35520-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/ebfca63379a4/srep35520-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/c10a9e0e6a22/srep35520-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/988837a69b33/srep35520-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/6c4004f0e9a2/srep35520-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/ba3c4389be04/srep35520-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/0ae5e1e5adb5/srep35520-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/6f1546e7b52d/srep35520-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/ebfca63379a4/srep35520-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/c10a9e0e6a22/srep35520-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/988837a69b33/srep35520-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/6c4004f0e9a2/srep35520-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/ba3c4389be04/srep35520-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd2/5067579/0ae5e1e5adb5/srep35520-f7.jpg

相似文献

1
Genome-wide analysis of alternative splicing during human heart development.人类心脏发育过程中可变剪接的全基因组分析。
Sci Rep. 2016 Oct 18;6:35520. doi: 10.1038/srep35520.
2
Global transcriptome analysis reveals extensive gene remodeling, alternative splicing and differential transcription profiles in non-seed vascular plant Selaginella moellendorffii.全球转录组分析揭示了非种子维管植物卷柏中广泛的基因重塑、可变剪接和差异转录谱。
BMC Genomics. 2017 Jan 25;18(Suppl 1):1042. doi: 10.1186/s12864-016-3266-1.
3
Systematic Characterization of Long Noncoding RNAs Reveals the Contrasting Coordination of Cis- and Trans-Molecular Regulation in Human Fetal and Adult Hearts.长链非编码RNA的系统表征揭示了人类胎儿和成人心脏中顺式和反式分子调控的对比协调。
Circ Cardiovasc Genet. 2016 Apr;9(2):110-8. doi: 10.1161/CIRCGENETICS.115.001264. Epub 2016 Feb 19.
4
High expression of long intervening non-coding RNA OLMALINC in the human cortical white matter is associated with regulation of oligodendrocyte maturation.长链居间非编码RNA OLMALINC在人皮质白质中的高表达与少突胶质细胞成熟的调控相关。
Mol Brain. 2015 Jan 10;8:2. doi: 10.1186/s13041-014-0091-9.
5
Genome-wide detection of testis- and testicular cancer-specific alternative splicing.全基因组范围内睾丸及睾丸癌特异性可变剪接的检测。
Carcinogenesis. 2007 Dec;28(12):2484-90. doi: 10.1093/carcin/bgm194. Epub 2007 Aug 27.
6
Read-Split-Run: an improved bioinformatics pipeline for identification of genome-wide non-canonical spliced regions using RNA-Seq data.读取-分割-运行：一种利用RNA测序数据识别全基因组非经典剪接区域的改进型生物信息学流程。
BMC Genomics. 2016 Aug 22;17 Suppl 7(Suppl 7):503. doi: 10.1186/s12864-016-2896-7.
7
Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.通过慢性淋巴细胞白血病标本的高通量RNA测序分析基因表达和剪接改变。
BMC Cancer. 2015 Oct 16;15:714. doi: 10.1186/s12885-015-1708-9.
8
Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells.与多能干细胞来源的心肌细胞相比的人类胎儿心脏转录组。
Development. 2015 Sep 15;142(18):3231-8. doi: 10.1242/dev.123810. Epub 2015 Jul 24.
9
Genome-wide analysis of alternative transcripts in human breast cancer.人类乳腺癌中可变转录本的全基因组分析。
Breast Cancer Res Treat. 2015 Jun;151(2):295-307. doi: 10.1007/s10549-015-3395-2. Epub 2015 Apr 26.
10
Identification of alternative splicing events regulated by an Arabidopsis serine/arginine-like protein, atSR45a, in response to high-light stress using a tiling array.利用基因芯片鉴定拟南芥丝氨酸/精氨酸丰富蛋白 atSR45a 响应高光胁迫调控的可变剪接事件。
Plant Cell Physiol. 2011 Oct;52(10):1786-805. doi: 10.1093/pcp/pcr115. Epub 2011 Aug 23.

引用本文的文献

1
Transcriptional regulation in heart development, disease and regeneration: reassessing the fetal gene hypothesis.心脏发育、疾病与再生中的转录调控：重新审视胎儿基因假说。
Nat Rev Cardiol. 2025 Sep 5. doi: 10.1038/s41569-025-01205-3.
2
Alternative splicing of the Snap23 microexon is regulated by MBNL, QKI, and RBFOX2 in a tissue-specific manner and is altered in striated muscle diseases.Snap23微小外显子的可变剪接由MBNL、QKI和RBFOX2以组织特异性方式调控，并在横纹肌疾病中发生改变。
RNA Biol. 2025 Dec;22(1):1-20. doi: 10.1080/15476286.2025.2491160. Epub 2025 May 6.
3
A Ratiometric Catalog of Protein Isoform Shifts in the Cardiac Fetal Gene Program.

本文引用的文献

1
Implications of the Wnt5a/CaMKII pathway in retinoic acid-induced myogenic tongue abnormalities of developing mice.Wnt5a/CaMKII信号通路在维甲酸诱导的发育中小鼠舌肌生成异常中的作用
Sci Rep. 2014 Aug 15;4:6082. doi: 10.1038/srep06082.
2
Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development.可变剪接在出生后心脏发育过程中调节心肌细胞中的囊泡运输基因。
Nat Commun. 2014 Apr 22;5:3603. doi: 10.1038/ncomms4603.
3
RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation.
心脏胎儿基因程序中蛋白质异构体变化的比例目录。
bioRxiv. 2024 Apr 10:2024.04.09.588716. doi: 10.1101/2024.04.09.588716.
4
Interrogations of single-cell RNA splicing landscapes with SCASL define new cell identities with physiological relevance.单细胞 RNA 剪接景观的剖析通过 SCASL 定义了具有生理相关性的新细胞身份。
Nat Commun. 2024 Mar 9;15(1):2164. doi: 10.1038/s41467-024-46480-9.
5
Rbfox1 controls alternative splicing of focal adhesion genes in cardiac muscle cells.Rbfox1 控制心肌细胞中黏着斑基因的可变剪接。
J Mol Cell Biol. 2024 Jul 1;16(1). doi: 10.1093/jmcb/mjae003.
6
Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.转录后修饰通过选择性剪接和致病性剪接变体在心血管发育和先天性心脏缺陷中的作用。
Int J Mol Sci. 2023 Jan 13;24(2):1555. doi: 10.3390/ijms24021555.
7
Cardiac splicing as a diagnostic and therapeutic target.心脏剪接作为诊断和治疗靶点。
Nat Rev Cardiol. 2023 Aug;20(8):517-530. doi: 10.1038/s41569-022-00828-0. Epub 2023 Jan 18.
8
RBPMS2 Is a Myocardial-Enriched Splicing Regulator Required for Cardiac Function.RBPMS2 是一种心肌特异性剪接调控因子，对于心脏功能至关重要。
Circ Res. 2022 Dec 2;131(12):980-1000. doi: 10.1161/CIRCRESAHA.122.321728. Epub 2022 Nov 11.
9
Transcription Factor GATA4 Regulates Cell Type-Specific Splicing Through Direct Interaction With RNA in Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitors.转录因子 GATA4 通过与人诱导多能干细胞衍生的心肌祖细胞中的 RNA 直接相互作用调节细胞类型特异性剪接。
Circulation. 2022 Sep 6;146(10):770-787. doi: 10.1161/CIRCULATIONAHA.121.057620. Epub 2022 Aug 8.
10
Maturation of hiPSC-derived cardiomyocytes promotes adult alternative splicing of SCN5A and reveals changes in sodium current associated with cardiac arrhythmia.人诱导多能干细胞衍生的心肌细胞的成熟促进 SCN5A 的成人选择性剪接，并揭示与心律失常相关的钠电流变化。
Cardiovasc Res. 2023 Mar 17;119(1):167-182. doi: 10.1093/cvr/cvac059.
RBM5、6 和 10 差异调控 NUMB 可变剪接以控制癌细胞增殖。
Mol Cell. 2013 Dec 12;52(5):720-33. doi: 10.1016/j.molcel.2013.11.010.
4
NONCODEv4: exploring the world of long non-coding RNA genes.NONCODEv4：探索长非编码 RNA 基因的世界。
Nucleic Acids Res. 2014 Jan;42(Database issue):D98-103. doi: 10.1093/nar/gkt1222. Epub 2013 Nov 26.
5
Regulation of alternative splicing by local histone modifications: potential roles for RNA-guided mechanisms.局部组蛋白修饰对可变剪接的调控：RNA 指导机制的潜在作用。
Nucleic Acids Res. 2014 Jan;42(2):701-13. doi: 10.1093/nar/gkt875. Epub 2013 Sep 29.
6
Genome-wide detection of condition-sensitive alternative splicing in Arabidopsis roots.在拟南芥根中进行全基因组条件敏感的可变剪接检测。
Plant Physiol. 2013 Jul;162(3):1750-63. doi: 10.1104/pp.113.217778. Epub 2013 Jun 4.
7
Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy.mRNA 测序鉴定出心脏肥大中胎儿剪接变异体的重新表达。
J Mol Cell Cardiol. 2013 Sep;62:99-107. doi: 10.1016/j.yjmcc.2013.05.004. Epub 2013 May 17.
8
Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-catenin signaling.长链非编码 RNA 与肝再生 1 相关，通过激活 Wnt/β-连环蛋白信号通路加速肝再生过程中的肝细胞增殖。
Hepatology. 2013 Aug;58(2):739-51. doi: 10.1002/hep.26361. Epub 2013 Jul 1.
9
Removal of retained introns regulates translation in the rapidly developing gametophyte of Marsilea vestita.保留内含子的去除调控了琉璃菜迅速发育的配子体中的翻译。
Dev Cell. 2013 Mar 11;24(5):517-29. doi: 10.1016/j.devcel.2013.01.015. Epub 2013 Feb 21.
10
Braveheart, a long noncoding RNA required for cardiovascular lineage commitment.勇敢的心，一种长非编码 RNA，对于心血管谱系的决定是必需的。
Cell. 2013 Jan 31;152(3):570-83. doi: 10.1016/j.cell.2013.01.003. Epub 2013 Jan 24.