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转录组数据分析揭示了再生斑马鱼心脏中共同的和损伤模型特异的基因表达变化。

Transcriptomic data meta-analysis reveals common and injury model specific gene expression changes in the regenerating zebrafish heart.

机构信息

Institute of Anatomy, University of Bern, 3012, Bern, Switzerland.

Department for Biomedical Research, University of Bern, 3012, Bern, Switzerland.

出版信息

Sci Rep. 2023 Apr 3;13(1):5418. doi: 10.1038/s41598-023-32272-6.

Abstract

Zebrafish have the capacity to fully regenerate the heart after an injury, which lies in sharp contrast to the irreversible loss of cardiomyocytes after a myocardial infarction in humans. Transcriptomics analysis has contributed to dissect underlying signaling pathways and gene regulatory networks in the zebrafish heart regeneration process. This process has been studied in response to different types of injuries namely: ventricular resection, ventricular cryoinjury, and genetic ablation of cardiomyocytes. However, there exists no database to compare injury specific and core cardiac regeneration responses. Here, we present a meta-analysis of transcriptomic data of regenerating zebrafish hearts in response to these three injury models at 7 days post injury (7dpi). We reanalyzed 36 samples and analyzed the differentially expressed genes (DEG) followed by downstream Gene Ontology Biological Processes (GO:BP) analysis. We found that the three injury models share a common core of DEG encompassing genes involved in cell proliferation, the Wnt signaling pathway and genes that are enriched in fibroblasts. We also found injury-specific gene signatures for resection and genetic ablation, and to a lower extent the cryoinjury model. Finally, we present our data in a user-friendly web interface that displays gene expression signatures across different injury types and highlights the importance to consider injury-specific gene regulatory networks when interpreting the results related to cardiac regeneration in the zebrafish. The analysis is freely available at: https://mybinder.org/v2/gh/MercaderLabAnatomy/PUB_Botos_et_al_2022_shinyapp_binder/HEAD?urlpath=shiny/bus-dashboard/ .

摘要

斑马鱼具有在受伤后完全再生心脏的能力,这与人类心肌梗死后心肌细胞不可逆转的丧失形成鲜明对比。转录组学分析有助于剖析斑马鱼心脏再生过程中的潜在信号通路和基因调控网络。该过程已在以下不同类型的损伤中进行了研究:心室切除、心室冷冻损伤和心肌细胞基因消融。然而,目前还没有数据库可以比较损伤特异性和核心心脏再生反应。在这里,我们对再生斑马鱼心脏在这三种损伤模型下的转录组数据进行了荟萃分析,损伤后 7 天(7dpi)。我们重新分析了 36 个样本,并对差异表达基因(DEG)进行了下游基因本体生物学过程(GO:BP)分析。我们发现这三种损伤模型具有一个共同的 DEG 核心,包含参与细胞增殖、Wnt 信号通路和富含成纤维细胞的基因的基因。我们还发现了切除和基因消融的损伤特异性基因特征,冷冻损伤模型的特征则较低。最后,我们以用户友好的 Web 界面呈现了我们的数据,该界面在不同的损伤类型之间显示了基因表达特征,并强调了当解释与斑马鱼心脏再生相关的结果时,考虑损伤特异性基因调控网络的重要性。该分析可在以下网址免费获取:https://mybinder.org/v2/gh/MercaderLabAnatomy/PUB_Botos_et_al_2022_shinyapp_binder/HEAD?urlpath=shiny/bus-dashboard/

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