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喜树碱处理早期斑马鱼胚胎的转录组效应数据集。

A dataset of transcriptomic effects of camptothecin treatment on early zebrafish embryos.

作者信息

Prykhozhij Sergey V, Ban Kevin, Brown Zane L, Kobar Kim, Wajnberg Gabriel, Fuller Charlotte, Chacko Simi, Lacroix Jacynthe, Crapoulet Nicolas, Midgen Craig, Shlien Adam, Malkin David, Berman Jason N

机构信息

Children's Hospital of Eastern Ontario (CHEO) Research Institute and University of Ottawa, Ottawa, ON, Canada.

Dalhousie University Medical School, Halifax, NS, Canada.

出版信息

Data Brief. 2024 Oct 16;57:111041. doi: 10.1016/j.dib.2024.111041. eCollection 2024 Dec.

DOI:10.1016/j.dib.2024.111041
PMID:39554546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11565048/
Abstract

Zebrafish () are a good model for cancer research including studies on chemotherapy treatments. We treated wild-type and deletion mutant zebrafish embryos at 24 h post-fertilization with 1 µM of the topoisomerase I inhibitor, camptothecin (CPT), for 4 h to catalogue gene expression changes induced by this DNA damage treatment and to understand if these changes are influenced by loss of miR-34a. The 4 sample groups of 3 independent biological samples consisting of 30 embryos each were analyzed by RNA-sequencing using the recently updated zebrafish transcriptome annotation based on GRCz11, which enabled a more complete and sensitive read mapping and gene assignment than standard annotations. Using this gene expression estimates dataset as the primary resource, we performed a differentially expressed gene (DEG) analysis based on treatment as loss of miR-34a had minimal effects on CPT-induced expression changes. The DEGs were analyzed for Gene Ontology and KEGG pathway terms. Enriched terms and pathways among up-regulated genes were mostly related to stress, cell death, cell cycle regulation, transcriptional regulation, cell signalling, developmental processes and synthesis of retinol and steroid hormones. By contrast, down-regulated genes were most strongly associated with genes involved in key developmental processes, adhesion molecules, as well as some transport and metabolic pathways, together suggesting a "developmental shutdown". We also identified interferon-regulated genes and p53 target genes activated or inhibited by DNA damage due to topoisomerase I inhibition, suggesting that they are important components of the response to this type of DNA damage in zebrafish embryos.

摘要

斑马鱼是癌症研究的良好模型,包括化疗治疗研究。我们在受精后24小时用1μM的拓扑异构酶I抑制剂喜树碱(CPT)处理野生型和miR-34a缺失突变体斑马鱼胚胎4小时,以梳理这种DNA损伤处理诱导的基因表达变化,并了解这些变化是否受miR-34a缺失的影响。由30个胚胎组成的4个样本组,每组有3个独立的生物学样本,使用基于GRCz11的最新更新的斑马鱼转录组注释通过RNA测序进行分析,与标准注释相比,这使得读取映射和基因分配更加完整和敏感。以这个基因表达估计数据集作为主要资源,我们基于处理进行了差异表达基因(DEG)分析,因为miR-34a的缺失对CPT诱导的表达变化影响最小。对差异表达基因进行了基因本体论和KEGG通路术语分析。上调基因中富集的术语和通路大多与应激、细胞死亡、细胞周期调控、转录调控、细胞信号传导、发育过程以及视黄醇和类固醇激素的合成有关。相比之下,下调基因与参与关键发育过程的基因、粘附分子以及一些运输和代谢通路密切相关,共同表明出现了“发育停滞”。我们还鉴定了因拓扑异构酶I抑制导致DNA损伤而被激活或抑制的干扰素调节基因和p53靶基因,表明它们是斑马鱼胚胎对这种类型DNA损伤反应的重要组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/580a953d01b9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/7c0d412d2c79/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/dc0994ce974d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/8b39656e6e48/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/580a953d01b9/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/7c0d412d2c79/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/dc0994ce974d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/8b39656e6e48/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c7a/11565048/580a953d01b9/gr4.jpg

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本文引用的文献

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PLoS Genet. 2024 May 28;20(5):e1011290. doi: 10.1371/journal.pgen.1011290. eCollection 2024 May.
2
Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential.传统的DNA损伤癌症疗法与新兴的cGAS-STING激活:关于免疫治疗潜力的综述与展望
Cancers (Basel). 2023 Aug 16;15(16):4127. doi: 10.3390/cancers15164127.
3
Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis.
斑马鱼成像是一种研究方法,通过它的观察可以发现,TP53 基因突变将致癌基因诱导的衰老从肿瘤抑制因子转变为肿瘤促进因子,从而促进了原发性肿瘤的发生。
Nat Commun. 2022 Mar 18;13(1):1417. doi: 10.1038/s41467-022-29061-6.
4
Camptothecin's journey from discovery to WHO Essential Medicine: Fifty years of promise.喜树碱从发现到世界卫生组织基本药物的历程:五十载承诺。
Eur J Med Chem. 2021 Nov 5;223:113639. doi: 10.1016/j.ejmech.2021.113639. Epub 2021 Jun 17.
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An improved zebrafish transcriptome annotation for sensitive and comprehensive detection of cell type-specific genes.改进的斑马鱼转录组注释,用于敏感和全面检测细胞类型特异性基因。
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