Ionizing radiation inhibits zebrafish embryo hatching through induction of tissue inhibitors of metalloproteinases (TIMPs) expression.

Eun Jung Kwon, Hansong Lee, Unbum Shin, Eun-Sun Kim, Kyungjae Myung, Jeongmo Kim, Jung-Hoon Park, Kihun Kim, Yoonsung Lee, Chang-Kyu Oh, Yun Hak Kim
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Abstract

Ionizing radiation (IR) has garnered growing attention because of its biological effects on aquatic organisms and humans. Here, we identify the most impacted organs and uncover the molecular mechanisms causing the changes in the context of vertebrate development using single-cell RNA sequencing. Alterations in cellular composition and biological functions were explored using transcriptomic profiling of zebrafish embryos exposed to 5 Gy. Single-cell RNA sequencing analyses unveiled notable shifts in the proportions of brain/central nervous system and hatching gland clusters. Although IR exposure led to increased expression of hatching enzymes, a significant but mild delay in hatching was observed following 5 Gy IR exposure. Gene Ontology analysis showed an increased expression of tissue inhibitors of metalloproteinases (TIMPs), known as matrix metalloproteinase inhibitors, which was confirmed via whole-mount in situ hybridization. Correlation analysis linked TIMPs to transcription factors cebpb and cebpd, which were significantly correlated post-IR exposure. Although no morphological changes were observed in some organs, including the brain, the study reveals substantial alterations in developing vertebrates. Notably, despite increased hatching enzymes, elevated TIMPs in the hatching gland suggest a regulatory mechanism impacting hatching activity. This research contributes to comprehending the ecological repercussions of IR exposure, emphasizing the importance of safety measures for aquatic ecosystems and overall environmental health.

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电离辐射通过诱导组织金属蛋白酶抑制剂(TIMPs)的表达抑制斑马鱼胚胎孵化。
电离辐射(IR)对水生生物和人类的生物影响日益受到关注。在这里,我们利用单细胞 RNA 测序技术确定了受影响最大的器官,并揭示了在脊椎动物发育过程中引起这些变化的分子机制。通过对暴露于 5 Gy 辐射的斑马鱼胚胎进行转录组分析,探讨了细胞组成和生物功能的变化。单细胞 RNA 测序分析揭示了大脑/中枢神经系统和孵化腺簇比例的显著变化。虽然红外暴露导致孵化酶的表达增加,但在暴露于 5 Gy 红外后,观察到孵化显著但轻微的延迟。基因本体分析表明,组织金属蛋白酶抑制剂(TIMPs)(又称基质金属蛋白酶抑制剂)的表达增加,这一点已通过全贴片原位杂交得到证实。相关性分析将 TIMPs 与转录因子 cebpb 和 cebpd 联系起来,这两种转录因子在暴露于红外线后有显著的相关性。虽然在包括大脑在内的一些器官中没有观察到形态学变化,但这项研究揭示了发育中脊椎动物的实质性改变。值得注意的是,尽管孵化酶增加,但孵化腺中 TIMPs 的升高表明存在影响孵化活动的调节机制。这项研究有助于理解红外暴露对生态的影响,强调了安全措施对水生生态系统和整体环境健康的重要性。
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