Advancing immunotoxicology with single-cell sequencing: Challenges and progress defining mechanisms of arsenic toxicity

Britton C. Goodale
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Abstract

Defining mechanisms of immunotoxicity is complicated by the many cell types that comprise the immune system, their phenotypic heterogeneity, distribution in tissues throughout the body, and complexity of in vivo interactions. Single-cell RNA-sequencing (scRNA-seq) methods hold promise for determining how chemical exposures alter gene expression and phenotype of individual immune cell phenotypes, leading to adverse effects on immune function. Using arsenic as a case study, this review will examine challenges in defining mechanisms of immunotoxicity and highlight findings from recent studies that have addressed immunotoxicological questions with scRNA-seq. Advancements in immunotherapeutic development driven by single-cell sequencing technologies will be discussed, along with how these state-of-the art methods may be applied to accelerate immunotoxicity testing in future studies. We will finally consider how cell-type-specific gene expression data can be leveraged to glean immune profiles from existing gene expression data, improving our understanding of immunotoxicity and ability to assess the health impacts of immunotoxic chemicals.

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利用单细胞测序推进免疫毒理学研究:挑战与进步 定义砷的毒性机制
由于组成免疫系统的细胞类型众多、表型不一、在全身组织中的分布以及体内相互作用的复杂性,确定免疫毒性的机制变得十分复杂。单细胞 RNA 测序(scRNA-seq)方法有望确定化学暴露如何改变基因表达和单个免疫细胞表型,从而对免疫功能产生不利影响。本综述将以砷为案例,探讨确定免疫毒性机制所面临的挑战,并重点介绍近期利用 scRNA-seq 解决免疫毒理学问题的研究结果。我们还将讨论单细胞测序技术在免疫疗法开发方面的进展,以及如何在未来的研究中应用这些最先进的方法来加速免疫毒性测试。最后,我们将探讨如何利用特定细胞类型的基因表达数据从现有的基因表达数据中收集免疫特征,从而提高我们对免疫毒性的认识和评估免疫毒性化学品对健康影响的能力。
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来源期刊
Current opinion in toxicology
Current opinion in toxicology Toxicology, Biochemistry
CiteScore
8.50
自引率
0.00%
发文量
0
审稿时长
64 days
期刊最新文献
Adverse outcome pathway networks as the basis for the development of new approach methodologies: Liver toxicity as a case study New approach methodologies (NAMs) in drug safety assessment: A vision of the future Editorial: Transforming toxicology one cell at a time: A special issue on the application of scRNA-seq to the study of environmental response Editorial Board Practical lessons of the 3Rs: Learning from the past and looking toward the future
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