单细胞测序技术在新污染物胚胎发育毒性研究中的应用:进展与展望

Application of single-cell sequencing technology to the study of embryonic developmental toxicity of emerging contaminants: Progress and perspectives

  • 摘要: 新污染物是一类具有生物蓄积性、环境持久性、高毒性等特点的环境化学物,长期蓄积会对环境和人体造成严重威胁。近年来广泛应用的单细胞RNA测序技术(scRNA-seq)可以通过分析单个细胞水平的转录组,揭示细胞类型的异质性和细胞间通讯的复杂性。在毒理学研究中,scRNA-seq技术已被用于识别不同细胞类型对污染物的响应以及污染物在胚胎发育过程中的作用机制,为深入研究新污染物的毒性机制提供了新的视角。本文综述了单细胞测序技术的分类、特点以及其在新污染物如全氟和多氟烷基化合物(PFAS)、抗生素和微塑料、邻苯二甲酸酯类与双酚类胚胎发育毒性中的应用,并探讨了当前研究的局限性和未来展望。单细胞测序技术可以通过细胞异质性分析和拟时序分析等方法探索和验证新污染物在胚胎发育中的具体毒性机制,但单细胞测序技术在新污染物毒性研究中仍面临挑战,包括数据集之间的偏倚、批次效应以及人类与模式生物之间的发育差异。未来研究需要进一步优化数据分析方法,整合多组学测序数据,并探索人类类器官模型在毒理学研究中的应用,以更全面地理解新污染物的毒性机制和长期健康影响,为新污染物全面严格管控提供理论依据。

     

    Abstract: Emerging pollutants are a class of environmental chemicals characterized by bioaccumulation, environmental persistence, and high toxicity. Their long-term accumulation poses severe threats to the environment and human health. In recent years, single-cell RNA sequencing (scRNA-seq) technology has enabled the analysis of transcriptomes at the single-cell level, revealing cellular heterogeneity and the complexity of intercellular communication. In toxicological studies, scRNA-seq technology has been applied to identify the responses of different cell types to pollutants and to elucidate the mechanisms of pollutant action during embryonic development, providing novel perspectives on the toxicity mechanisms of emerging pollutants. This paper reviewed the classification and characteristics of single-cell sequencing technologies and their applications in investigating the developmental toxicity of emerging pollutants, including perfluorinated and polyfluorinated alkyl substances (PFAS), antibiotics, microplastics, phthalates, and bisphenols. It also discussed the limitations of current studies and proposed future research directions. Through methods such as cellular heterogeneity analysis and pseudotemporal chronological analysis, single-cell sequencing can explore and validate the specific toxicity mechanisms of emerging pollutants in embryonic development. However, challenges remain, including dataset bias, batch effects, and developmental differences between humans and model organisms. Future research should focus on optimizing data analysis methods, integrating multi-omics sequencing data, and exploring the use of human organoid models in toxicological studies. Such efforts will contribute to a more comprehensive understanding of the toxicity mechanisms and long-term health impacts of emerging pollutants, providing a theoretical basis for their stringent regulation and control.

     

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