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心脏和脑组织中缺氧及复氧后的转录组图谱:对基因表达、可变剪接和信号通路的见解

Transcriptomic atlas for hypoxia and following re-oxygenation in heart and brain tissues: insights into gene expression, alternative splicing, and signaling pathways.

作者信息

Chen Jian, Hu Zhen, Li Pei, Wang Guiying, Wei Huijie, Li Qing, Fu Beide, Sun Yanhong

机构信息

Fisheries Research Institute, Wuhan Academy of Agricultural Sciences, Wuhan, China.

Hubei Provincial Fisheries Technology Extension Center, Wuhan, China.

出版信息

Front Genet. 2024 Apr 16;15:1365285. doi: 10.3389/fgene.2024.1365285. eCollection 2024.

DOI:10.3389/fgene.2024.1365285
PMID:38689653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11058841/
Abstract

Hypoxia is a mounting problem that affects the world's freshwaters, with severe consequence for many species, including death and large economical loss. The hypoxia problem has increased recently due to the combined effects of water eutrophication and global warming. In this study, we investigated the transcriptome atlas for the bony fish under hypoxia for 1.5, 3, and 4.5 h and its recovery to normal oxygen levels in heart and brain tissues. We sequenced 21 samples for brain and heart tissues (a total of 42 samples) plus three control samples and obtained an average of 32.40 million raw reads per sample, and 95.24% mapping rate of the filtered clean reads. This robust transcriptome dataset facilitated the discovery of 52,428 new transcripts and 6,609 novel genes. In the heart tissue, the KEGG enrichment analysis showed that genes linked to the Vascular smooth muscle contraction and MAPK and VEGF signaling pathways were notably altered under hypoxia. Re-oxygenation introduced changes in genes associated with abiotic stimulus response and stress regulation. In the heart tissue, weighted gene co-expression network analysis pinpointed a module enriched in insulin receptor pathways that was correlated with hypoxia. Conversely, in the brain tissue, the response to hypoxia was characterized by alterations in the PPAR signaling pathway, and re-oxygenation influenced the mTOR and FoxO signaling pathways. Alternative splicing analysis identified an average of 27,226 and 28,290 events in the heart and brain tissues, respectively, with differential events between control and hypoxia-stressed groups. This study offers a holistic view of transcriptomic adaptations in heart and brain tissues under oxygen stress and emphasizes the role of gene expression and alternative splicing in the response mechanisms.

摘要

缺氧是一个日益严重的问题,影响着全球的淡水,给包括死亡和巨大经济损失在内的许多物种带来了严重后果。由于水体富营养化和全球变暖的综合影响,缺氧问题最近有所加剧。在本研究中,我们调查了硬骨鱼在缺氧1.5小时、3小时和4.5小时以及恢复到正常氧水平时心脏和脑组织的转录组图谱。我们对21个脑和心脏组织样本(共42个样本)以及3个对照样本进行了测序,每个样本平均获得3240万个原始读数,过滤后的干净读数的映射率为95.24%。这个强大的转录组数据集有助于发现52428个新转录本和6609个新基因。在心脏组织中,KEGG富集分析表明,与血管平滑肌收缩、MAPK和VEGF信号通路相关的基因在缺氧条件下发生了显著变化。复氧导致了与非生物刺激反应和应激调节相关基因的变化。在心脏组织中,加权基因共表达网络分析确定了一个富含胰岛素受体途径的模块,该模块与缺氧相关。相反,在脑组织中,对缺氧的反应以PPAR信号通路的改变为特征,而复氧影响了mTOR和FoxO信号通路。可变剪接分析分别在心脏和脑组织中平均鉴定出27226个和28290个事件,对照组和缺氧应激组之间存在差异事件。本研究提供了氧应激下心脏和脑组织转录组适应性的整体视图,并强调了基因表达和可变剪接在反应机制中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/482bdcfb27ce/fgene-15-1365285-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/392d4d67883b/fgene-15-1365285-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/86c5e508da27/fgene-15-1365285-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/2fa02df8af54/fgene-15-1365285-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/482bdcfb27ce/fgene-15-1365285-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/392d4d67883b/fgene-15-1365285-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/86c5e508da27/fgene-15-1365285-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/2fa02df8af54/fgene-15-1365285-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad00/11058841/482bdcfb27ce/fgene-15-1365285-g004.jpg

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Alternative splicing plays key roles in response to stress across different stages of fighting in the fish Betta splendens.可变剪接在鱼类斗斗鱼不同战斗阶段对压力的反应中起着关键作用。
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