Department of Pharmacology, Korea University College of Medicine, Seoul, 02481, Republic of Korea.
Receptor.AI Inc., 16192 Coastal Highway, County of Sussex, Lewes, DE, 19958, USA.
Sci Rep. 2022 Mar 18;12(1):4660. doi: 10.1038/s41598-022-08799-5.
Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) has been suspected to cause toxicity invertebrates, but its phenotypic effects and the underlying regulatory mechanism have not been fully revealed. Generally, cellular responses tightly control and affect various phenotypes. The scope of the whole organism or cellular toxicological phenotyping, however, has been limited, and quantitative analysis methods using phenotype data have not been fully established. Here, we demonstrated that fluorescence imaging of sub-organelle-based phenomic analysis together with transcriptomic profiling can enable a comprehensive understanding of correlations between molecular and phenomic events. To reveal the cellular response to TDCPP exposure, we obtained three sub-organelle images as fluorescent phenotypes. Transcriptomic perturbation data were measured from the RNA-seq experiment, and both profiling results were analyzed together. Interestingly, organelle phenomic data showed a unique fluorescent intensity increase in the endoplasmic reticulum (ER), and pathway analysis using transcriptomic data also revealed that ER was significantly enriched in gene ontology terms. Following the series of analyses, RNA-seq data also revealed potential carcinogenic effects of TDCPP. Our multi-dimensional profiling approach for organophosphate chemicals can uniquely correlate phenotypic changes with transcriptomic perturbations.
磷酸三(1,3-二氯丙基)酯(TDCPP)已被怀疑对无脊椎动物具有毒性,但它的表型效应和潜在的调控机制尚未完全揭示。通常,细胞反应会严格控制和影响各种表型。然而,整个生物体或细胞毒性表型的范围受到限制,并且尚未充分建立使用表型数据的定量分析方法。在这里,我们证明了基于亚细胞器的表型分析的荧光成像与转录组分析相结合,可以全面了解分子和表型事件之间的相关性。为了揭示细胞对 TDCPP 暴露的反应,我们获得了三个亚细胞器图像作为荧光表型。从 RNA-seq 实验中测量了转录组扰动数据,并一起分析了这两种分析结果。有趣的是,细胞器表型数据显示内质网(ER)的荧光强度增加具有独特性,转录组数据的通路分析也表明 ER 在基因本体论术语中显著富集。经过一系列分析,RNA-seq 数据还揭示了 TDCPP 的潜在致癌作用。我们对有机磷化学物质的多维分析方法可以将表型变化与转录组扰动独特地相关联。