Philip Moos, Jenna Cheminant, Ujjwal Adhikari, Alessandro Venosa
{"title":"Transcriptomic-based roadmap to the healthy and ozone-exposed lung","authors":"Philip Moos, Jenna Cheminant, Ujjwal Adhikari, Alessandro Venosa","doi":"10.1016/j.cotox.2023.100445","DOIUrl":"10.1016/j.cotox.2023.100445","url":null,"abstract":"<div><p>The lung is constantly exposed to a myriad of exogenous stressors. Ground-level ozone represents a ubiquitous and extremely reactive anthropogenic toxicant, impacting the health of millions across the globe. While abundant, epidemiological, <em>in vivo</em>, and <em>in vitro</em> data focuses the ozone toxicity in individual cell types (e.g. epithelial type II, alveolar macrophages) or signaling pathways involved in the injury (e.g. akt, glutathione). When appropriately used, bulk and single-cell RNA sequencing techniques have the potential to provide complete, and in certain cases unbiased, information of the molecular events taking place in the steady-state and injured lung, and even capture the phenotypic diversity of neighboring cells. To this end, this review compiles information pertaining to the latest understanding of lung cell identity and activation in the steady-state and ozone-exposed lung. In addition, it discusses the value and benefits of multi-omics approaches and other tools developed to predict cell–cell communication and dissect spatial heterogeneity.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"37 ","pages":"Article 100445"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468202023000608/pdfft?md5=c638bcf1fa63e7c44f50b43e2c986646&pid=1-s2.0-S2468202023000608-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138529934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring the mixture assessment or allocation factor (MAF): A brief overview of the current discourse","authors":"Thomas Backhaus","doi":"10.1016/j.cotox.2024.100460","DOIUrl":"10.1016/j.cotox.2024.100460","url":null,"abstract":"<div><p>The European Chemicals Strategy for Sustainability requests to include a mixture assessment factor (MAF) into the safety assessment of chemicals, in order to account for the elevated risks of chemical mixtures. This text first reflects on the conceptual background of the MAF, and then provides an overview of current stakeholder positions and of the studies attempting to quantify an appropriate size of the MAF.</p><p>Stakeholders from industry, civil society organizations (NGOs), and regulatory authorities have already put forth statements regarding the perceived advantages and disadvantages of the MAF approach, sometimes without providing detailed arguments. A consensus seems to emerge that the so-called MAF<sub>factor</sub> is not a suitable instrument, due to its indiscriminatory nature that penalizes even chemicals that contribute only marginally to the mixture risk. Members of the larger MAF<sub>ceiling</sub> family, in particular the MAF<sub>exact,</sub> overcome this limitation and are therefore suggested as the way forward.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"37 ","pages":"Article 100460"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single cell approaches to understand environmental impacts on aggressive breast cancers","authors":"David Aguilar Jr. , Justin A. Colacino","doi":"10.1016/j.cotox.2024.100459","DOIUrl":"10.1016/j.cotox.2024.100459","url":null,"abstract":"<div><p><span>Breast cancer is a heterogeneous suite of diseases, with likely strong, but still poorly understood, environmental etiologies. New advances in single cell methods are now poised to help us understand how environmental exposures, such as air and water pollutants, diet, personal and consumer care products, and social factors, may promote the development of aggressive breast cancers. In this review, we describe how dissociated and spatial single cell transcriptomic analyses can be used to advance our understanding how our environment impacts </span>breast carcinogenesis through the view of frameworks such as the Hallmarks of Cancer and the Key Characteristics of Carcinogens.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"37 ","pages":"Article 100459"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of single cell gene expression technologies to neurotoxicology","authors":"Anke M. Tukker, Aaron B. Bowman","doi":"10.1016/j.cotox.2023.100458","DOIUrl":"10.1016/j.cotox.2023.100458","url":null,"abstract":"<div><p>Neurotoxicological research faces the challenge of linking biological changes resulting from exposures to neuronal function. An additional challenge is understanding cell-type-specific differences and selective vulnerabilities of distinct neuronal populations to toxic insults. Single-cell RNA-sequencing (scRNA-seq) allows for measurement of the transcriptome<span> of individual cells. This makes it a valuable tool for validating and characterizing cell types present in multi-cell type samples in complex tissue or cell culture models, but also for understanding how different cell types respond to toxic insults. Pathway analysis of differentially expressed genes can provide in-depth insights into underlying cell-type-specific mechanisms of neurotoxicity<span>. Toxicological data often has to be translated to outcomes for human health which requires an understanding of inter-species differences. Transcriptomic data aids in understanding these differences, including understanding the developmental timelines of different species. We believe that scRNA-seq holds exciting promises for future neurotoxicological research.</span></span></p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"37 ","pages":"Article 100458"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139051464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junhui Chen , Jiangpeng Wu , Yunmeng Bai , Chuanbin Yang , Jigang Wang
{"title":"Recent advances of single-cell RNA sequencing in toxicology research: Insight into hepatotoxicity and nephrotoxicity","authors":"Junhui Chen , Jiangpeng Wu , Yunmeng Bai , Chuanbin Yang , Jigang Wang","doi":"10.1016/j.cotox.2024.100462","DOIUrl":"10.1016/j.cotox.2024.100462","url":null,"abstract":"<div><p><span>The advanced single-cell RNA sequencing (scRNA-seq) technology enables the measurement of </span>gene expression levels<span> and identification of cell-specific markers in individual cells, and the revealing of cell types, providing valuable insights into cell behavior. ScRNA-seq has emerged as an effective method for detecting rare cell populations, cellular heterogeneity, and cell-to-cell crosstalk under physiology and pathology conditions, thereby advancing the revolution of toxicology research. In this review, we first briefly introduce the concept of hepatotoxicity and nephrotoxicity, along with their underlying mechanisms. We then summarize the single-cell sequencing technology, with an emphasis on single-cell isolation techniques, particularly for the most used droplet-based methods. Finally, we review the recent advances in the application of single-cell RNA sequencing in studying hepatotoxicity and nephrotoxicity. Overall, this review provides a comprehensive understanding of the recent advances in hepatotoxicity and nephrotoxicity studies at a single-cell resolution.</span></p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"37 ","pages":"Article 100462"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139474840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing immunotoxicology with single-cell sequencing: Challenges and progress defining mechanisms of arsenic toxicity","authors":"Britton C. Goodale","doi":"10.1016/j.cotox.2024.100461","DOIUrl":"10.1016/j.cotox.2024.100461","url":null,"abstract":"<div><p><span><span>Defining mechanisms of immunotoxicity is complicated by the many cell types that comprise the immune system, their </span>phenotypic heterogeneity, distribution in tissues throughout the body, and complexity of </span><em>in vivo</em><span> interactions. Single-cell RNA-sequencing (scRNA-seq) methods hold promise for determining how chemical exposures alter gene expression and phenotype of individual immune cell<span> 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.</span></span></p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"37 ","pages":"Article 100461"},"PeriodicalIF":4.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139458681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dylan Hatai, Max T. Levenson, V. Rehan, Patrick Allard
{"title":"Inter- and trans-generational impacts of environmental exposures on the germline resolved at the single-cell level","authors":"Dylan Hatai, Max T. Levenson, V. Rehan, Patrick Allard","doi":"10.1016/j.cotox.2024.100465","DOIUrl":"https://doi.org/10.1016/j.cotox.2024.100465","url":null,"abstract":"","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"18 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139883636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}