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解码细胞应激状态的毒理学使用单细胞转录组学.

Imran Shah1, David Gallegos1, Brian Robinette1

  • 1Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.

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|August 6, 2025
PubMed
概括
此摘要是机器生成的。

单细胞转录组学揭示了各种细胞对化学物质的应激反应,确定了五种不同的细胞状态,从稳态到亡. 这种方法有助于理解毒理途径和适应性细胞过渡.

关键词:
这就是HepaRGG.适应性应激反应是一种适应性应激反应.细胞状态 细胞状态细胞结构过渡图表.计算毒理学计算毒理学单细胞转录基因组学 (SCTr)

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科学领域:

  • 毒理学 毒理学 毒理学
  • 细胞生物学 细胞生物学
  • 基因组学就是基因组学.

背景情况:

  • 了解细胞对化学物质暴露的反应对于毒理学至关重要.
  • 适应性应激反应通路 (SRPs) 在细胞生存和死亡中起着关键作用.
  • 单细胞转录组 (SCTr) 分析为研究细胞异质性提供了高分辨率.

研究的目的:

  • 使用SCTr. 用于在HepaRG细胞中描述适应性应激反应通路 (SRPs).
  • 在单细胞水平上研究细胞对各种化学压力因素的反应.
  • 在化学暴露期间识别不同的细胞表型状态和转变.

主要方法:

  • 应用了TempO-LINC®平台对约40,000个HepaRG细胞进行SCTr分析.
  • 暴露在细胞中的埃托波西德,布雷菲尔丁A,循环赫西米德,罗特,tBHQ,特洛格利塔和图尼卡米辛.
  • 使用SRP基因特征得分的细胞和使用一般化的Jaccard指标集群的表型.

主要成果:

  • 确定了五个不同的表型群体:恒常,适应性反应,终端结果,自和亡.
  • 观察到对化学物质的异质反应,其中UPR,OSR,HSR和DDR等特定途径被激活.
  • 特洛格利塔上调脂质代谢和HSR/UPR;布雷菲尔丁A/图尼卡米辛诱导UPR;罗激发了线粒体应激反应.

结论:

  • SCTr对于解码细胞应激状态和异质性是有价值的.
  • 该研究提供了关于细胞适应和毒性之间的过渡的见解.
  • 这种方法可以阐明化学诱导的细胞死亡背后的机制.