Proteogenomics Integrating Reveal a Complex Network, Alternative Splicing, Hub Genes Regulating Heart Maturation.

Proteogenomics Integrating Reveal a Complex Network, Alternative Splicing, Hub Genes Regulating Heart Maturation.
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蛋白质基因组学整合揭示了调节心脏成熟的复杂网络、选择性剪接、枢纽基因

DOI:
10.3390/genes13020250
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发表时间:
2022-01-28
期刊:
影响因子:
3.5
通讯作者:
Zhang G
Zhang G
中科院分区:
生物学3区
文献类型:
--
作者:
Yang H;Liu W;Song S;Bai L;Nie Y;Bai Y;Zhang G

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心脏成熟是新生儿心脏向成人心脏转变的本质生物学过程,因此阐明心脏成熟的机制可能有助于探讨出生后心脏发育和心肌病。这项研究结合了基于同量异位标签的相对和绝对定量 (iTRAQ) 的蛋白质组分析和基于 RNA 测序的转录组分析,以检测与小鼠心脏成熟相关的蛋白质和基因。蛋白质基因组学整合分析确定了 254 个基因/蛋白质在新生儿和成人心脏之间普遍存在差异表达。功能和通路分析表明,这些已识别的基因/蛋白质主要通过调节 mRNA 加工和能量代谢来促进心脏成熟。全基因组选择性剪接 (AS) 分析表明,一些重要的肌节和能量相关基因经历不同的 AS 事件。通过Cytoscape插件CytoHubba共发现23个hub基因,并通过RT-qPCR进一步证实。接下来,我们通过检测 Ogdhl 干扰心肌细胞中的能量代谢表型变化,证实上调最多的枢纽基因 Ogdhl 在心脏成熟中发挥重要作用。我们共同揭示了一个复杂的基因网络、AS 基因和模式,以及通过蛋白质组和转录组组合分析控制心脏成熟的候选中心基因。
Heart maturation is an essentially biological process for neonatal heart transition to adult heart, thus illustrating the mechanism of heart maturation may be helpful to explore postnatal heart development and cardiac cardiomyopathy. This study combined proteomic analysis based on isobaric tags for relative and absolute quantitation (iTRAQ) and transcriptome analysis based on RNA sequencing to detect the proteins and genes associated with heart maturation in mice. The proteogenomics integrating analysis identified 254 genes/proteins as commonly differentially expressed between neonatal and adult hearts. Functional and pathway analysis demonstrated that these identified genes/proteins contribute to heart maturation mainly by regulating mRNA processing and energy metabolism. Genome-wide alternative splicing (AS) analysis showed that some important sarcomere and energy-associated genes undergo different AS events. Through the Cytoscape plug-in CytoHubba, a total of 23 hub genes were found and further confirmed by RT-qPCR. Next, we verified that the most up-regulated hub gene, Ogdhl, plays an essential role in heart maturation by detecting energy metabolism phenotype changes in the Ogdhl-interfering cardiomyocytes. Together, we revealed a complex gene network, AS genes and patterns, and candidate hub genes controlling heart maturation by proteome and transcriptome combination analysis.
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