Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure.
Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure.
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全长转录组测序：深入了解狗心力衰竭模型
DOI：
10.3389/fcvm.2021.712797
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发表时间：
2021
影响因子：
3.6
通讯作者：
Tang B
中科院分区：
文献类型：
--
作者：
Liang X;Bai Z;Wang F;Han Y;Sun H;Xiaokereti J;Zhang L;Zhou X;Lu Y;Tang B
心力衰竭（HF）导致发病率和死亡率的逐渐增加。本研究旨在探索HF期间的转录景观，并识别与HF相关的差异表达转录物（DETs）和其他剪接事件。我们使用右心室起搏器植入建立了一个HF狗模型（n = 3）。我们对心肌组织进行了全长转录组测序（基于纳米孔平台），并使用差异表达分析和功能注释方法分析转录本[基因本体（GO）和京都基因与基因组百科全书（KEGG）分析]。此外，我们通过实时荧光定量PCR （qRT-PCR）估计所选基因的表达，并使用流式细胞术检测免疫细胞的比例。我们发现b型利钠肽升高，射血分数降低，心衰犬模型有明显的临床症状。我们使用全长转录组测序鉴定了67,458个转录本。HF组和对照组共获得785个det。这些DETs主要富集于免疫应答，特别是Th1、Th2和Th17细胞分化过程。此外，流式细胞术结果显示，与对照组相比，HF患者中Th1和Th17细胞的比例增加，而Th2细胞的比例下降。采用qRT-PCR定量分析HF组和对照组中与Th1、Th2和Th17细胞分化相关的差异表达基因。我们还发现了肌瘤基因的可变剪接事件（例如，MYBPC3, TNNT2， TTN， FLNC和TTNI3）。此外，我们检测到4892个转录因子和406个与HF相关的lncrna。我们基于全长转录本测序的分析为犬HF模型提供了一个分析视角，这对日益相关的HF大型动物模型的分子研究具有重要价值。
Heart failure (HF) leads to a progressive increase in morbidity and mortality rates. This study aimed to explore the transcriptional landscape during HF and identify differentially expressed transcripts (DETs) and alternative splicing events associated with HF. We generated a dog model of HF (n = 3) using right ventricular pacemaker implantation. We performed full-length transcriptome sequencing (based on nanopore platform) on the myocardial tissues and analyzed the transcripts using differential expression analysis and functional annotation methods [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses]. Additionally, we estimated the expression of the selected genes by quantitative real-time PCR (qRT-PCR) and detected the proportion of immune cells using flow cytometry. We found that increased B-type natriuretic peptide reduced ejection fraction, and apparent clinical signs were observed in the dog model of HF. We identified 67,458 transcripts using full-length transcriptome sequencing. A total of 785 DETs were obtained from the HF and control groups. These DETs were mainly enriched in the immune responses, especially Th1, Th2, and Th17 cell differentiation processes. Furthermore, flow cytometry results revealed that the proportion of Th1 and Th17 cells increased in patients with HF compared to controls, while the proportion of Th2 cells decreased. Differentially expressed genes in the HF and control groups associated with Th1, Th2, and Th17 cell differentiation were quantified using qRT-PCR. We also identified variable splicing events of sarcomere genes (e.g., MYBPC3, TNNT2, TTN, FLNC, and TTNI3). In addition, we detected 4,892 transcription factors and 406 lncRNAs associated with HF. Our analysis based on full-length transcript sequencing provided an analysis perspective in a dog model of HF, which is valuable for molecular research in an increasingly relevant large animal model of HF.
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影响因子：
4.6
作者：
Gröschel C;Sasse A;Röhrborn C;Monecke S;Didié M;Elsner L;Kruse V;Bunt G;Lichtman AH;Toischer K;Zimmermann WH;Hasenfuß G;Dressel R
通讯作者：
Dressel R
影响因子：
5.3
作者：
Fan Z;Gao S;Chen Y;Xu B;Yu C;Yue M;Tan X
通讯作者：
Tan X
DOI：
10.1038/nrm.2017.27
发表时间：
2017-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Baralle FE;Giudice J
通讯作者：
Giudice J
DOI：
10.3390/ani10101906
发表时间：
2020-10-18
期刊：
Animals : an open access journal from MDPI
影响因子：
--
作者：
Charles CJ;Rademaker MT;Scott NJA;Richards AM
通讯作者：
Richards AM
影响因子：
10.8
作者：
Kay, Maryam;Soltani, Bahram M.;Pedrazzini, Thierry
通讯作者：
Pedrazzini, Thierry