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首页> 外文期刊>Journal of Hazardous Materials >Genome-wide CRISPR-Cas9 screening in Bombyx mori reveals the toxicological mechanisms of environmental pollutants, fluoride and cadmium
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Genome-wide CRISPR-Cas9 screening in Bombyx mori reveals the toxicological mechanisms of environmental pollutants, fluoride and cadmium

机译：Bombyx Mori在Bombyx Mori筛选的基因组 - 范围内Carp-Cas9揭示了环境污染物，氟化物和镉的毒理机制

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摘要

Fluoride and cadmium, two typical environmental pollutants, have been extensively existed in the ecosystem and severely injured various organisms including humans. To explore the toxicological properties and the toxicological mechanism of fluoride and cadmium in silkworm, we perform a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) -based functional genomic screen, which can directly measure the genetic requirement of genes in response to the pollutants. Our screen identifies 751 NaF-resistance genes, 753 NaF-sensitive genes, 757 CdCl2-resistance genes, and 725 CdCl2-sensitive genes. The top-ranked resistant genes are experimentally verified and the results show that their loss conferred resistance to fluoride or cadmium. Functional analysis of the resistant- and sensitive-genes demonstrates enrichment of multiple signaling pathways, among which the MAPK signaling pathway and DNA damage and repair are both required for fluoride- or cadmiuminduced cell death, whereas the Toll and Imd signaling pathway and Autophagy are fluoride- or cadmiumspecific. Moreover, we confirm that these pathways are truly involved in the toxicological mechanism in both cultured cells and individual tissues. Our results supply potential targets for rescuing the biohazards of fluoride and cadmium in silkworm, and reveal the feasible toxicological mechanism, which highlights the role of functional genomic screens in elucidating the toxicity mechanisms of environmental pollutants.
机译：氟化物和镉，两个典型的环境污染物，在生态系统中已广泛存在，并且严重受伤，包括人类在内的各种生物。为了探讨泌虫和镉的毒理学特性和毒理学机制，我们进行CRISPR（常规间隙的短语重复）基础的功能基因组筛选，可直接测量基因的遗传要求响应污染物。我们的筛选鉴定了751个Naf抗性基因，753个Naf敏感基因，757个CdCl2抗性基因和725cCl2敏感基因。通过实验验证排名抗性基因，结果表明，它们的损失赋予氟化物或镉的抵抗力。抗性和敏感基因的功能分析表明了多种信号通路的富集，其中MAPK信号通路和DNA损伤和修复都需要氟化物或镉诱导的细胞死亡，而损失和IMD信号通路和自噬是氟化物 - 或cadmiumpectific。此外，我们确认这些途径真正参与培养细胞和个体组织中的毒理机制。我们的结果提供了拯救蚕豆生物胆碱和蚕豆生物危害的潜在目标，并揭示了可行的毒理学机制，突出了功能基因组筛查阐明了环境污染物的毒性机制。

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  • 来源
    《Journal of Hazardous Materials》 |2021年第15期|124666.1-124666.11|共11页
  • 作者

    Liu Yue; Chang Jiasong; Yang Chengfei; Zhang Tong; Chen Xiaoxu; Shi Run; Liang Yan; Xia Qingyou; Ma Sanyuan;

  • 作者单位

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Army Med Univ Affiliated Hosp 2 Dept Urol Chongqing 400037 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

    Southwest Univ State Key Lab Silkworm Genome Biol Chongqing 400716 Peoples R China|Southwest Univ Biol Sci Res Ctr Chongqing 400716 Peoples R China|Southwest Univ Chongqing Engn & Technol Res Ctr Novel Silk Mat Chongqing 400716 Peoples R China|Southwest Univ Chongqing Key Lab Sericulture Chongqing 400716 Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Cadmium; CRISPR; Fluoride; Genomic screening; Silkworm; Toxicological mechanism;

    机译：镉;CRISPR;氟化物;基因组筛查;蚕;毒理机制;

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