Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP9297 |
Quality Control for Single Cell Imaging Analytics Using Endocrine Disruptor-Induced Changes in Estrogen Receptor Expression | |
Fabio Stossi; Pankaj K. Singh; Ragini M. Mistry; Hannah L. Johnson; Radhika D. Dandekar; Maureen G. Mancini; Adam T. Szafran; Arvind U. Rao; Michael A. Mancini | |
2022-02-15 | |
发表期刊 | Environmental Health Perspectives
![]() |
出版年 | 2022 |
英文摘要 | AbstractBackground:Diverse toxicants and mixtures that affect hormone responsive cells [endocrine disrupting chemicals (EDCs)] are highly pervasive in the environment and are directly linked to human disease. They often target the nuclear receptor family of transcription factors modulating their levels and activity. Many high-throughput assays have been developed to query such toxicants; however, single-cell analysis of EDC effects on endogenous receptors has been missing, in part due to the lack of quality control metrics to reproducibly measure cell-to-cell variability in responses. Objective:We began by developing single-cell imaging and informatic workflows to query whether the single cell distribution of the estrogen (ER), used as a model system, can be used to measure effects of EDCs in a sensitive and reproducible manner. Methods:We used high-throughput microscopy, coupled with image analytics to measure changes in single cell ER nuclear levels on treatment with toxicants, over a large number of biological and technical replicates. Results:We developed a two-tiered quality control pipeline for single cell analysis and tested it against a large set of biological replicates, and toxicants from the EPA and Agency for Toxic Substances and Disease Registry lists. We also identified a subset of potentially novel EDCs that were active only on the endogenous ER level and activity as measured by single molecule RNA fluorescence in situ hybridization (RNA FISH). Discussion:We demonstrated that the distribution of ER levels per cell, and the changes upon chemical challenges were remarkably stable features; and importantly, these features could be used for quality control and identification of endocrine disruptor toxicants with high sensitivity. When coupled with orthogonal assays, ER single cell distribution is a valuable resource for high-throughput screening of environmental toxicants. https://doi.org/10.1289/EHP9297 |
领域 | 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/346641 |
专题 | 资源环境科学 |
推荐引用方式 GB/T 7714 | Fabio Stossi,Pankaj K. Singh,Ragini M. Mistry,et al. Quality Control for Single Cell Imaging Analytics Using Endocrine Disruptor-Induced Changes in Estrogen Receptor Expression[J]. Environmental Health Perspectives,2022. |
APA | Fabio Stossi.,Pankaj K. Singh.,Ragini M. Mistry.,Hannah L. Johnson.,Radhika D. Dandekar.,...&Michael A. Mancini.(2022).Quality Control for Single Cell Imaging Analytics Using Endocrine Disruptor-Induced Changes in Estrogen Receptor Expression.Environmental Health Perspectives. |
MLA | Fabio Stossi,et al."Quality Control for Single Cell Imaging Analytics Using Endocrine Disruptor-Induced Changes in Estrogen Receptor Expression".Environmental Health Perspectives (2022). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论