Dataset Information

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

ABSTRACT:

Background

Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown.

Methods

Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo animal studies, we analyzed the liver tissues from untreated and GLY-treated mice.

Results

We generated the first scRNA-seq atlas of GLY-exposed mouse liver. GLY induced varied cell composition, shared or cell-type-specific transcriptional alterations, and dysregulated cell-cell communication and thus exerted hepatotoxicity effects. The oxidative stress and inflammatory response were commonly upregulated in several cell types. We also observed activation and upregulated phagocytosis in macrophages, as well as proliferation and extracellular matrix overproduction in hepatic stellate cells.

Conclusions

Our study provides a comprehensive single-cell transcriptional picture of the toxic effect of GLY in the liver, which offers novel insights into the molecular mechanisms of the GLY-associated hepatotoxicity.

SUBMITTER: Wu J

PROVIDER: S-EPMC9898913 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

Wu Jiangpeng J Sun Xiuping X Wu Chunyi C Hong Xiaoping X Xie Lulin L Shi Zixu Z Zhao Liang L Du Qingfeng Q Xiao Wei W Sun Jichao J Wang Jigang J

Cellular & molecular biology letters 20230204 1

<h4>Background</h4>Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown.<h4>Methods</h4>Using single-cell RNA sequencing (scRNA-seq), immunofluorescent staining, and in vivo ...[more]

PMID: 36739397

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Project description:BackgroundCombinatory therapeutic strategy containing immunochemotherapy as part of induction therapy components is one of the current trends in the treatment of high-risk metastatic locally advanced nasopharyngeal carcinoma (NPC). However, the mechanism underlying the heterogeneity of response at the single-cell level has not been underexplored.Methods18 bulks and 11 single-cell RNA sequencing from paired before-treatment and on-treatment samples in patients with treatment-naive high-risk metastatic locally advanced NPCs were obtained. Following quality control, a total of 87 191 cells were included in the subsequence bioinformatics analysis.ResultsImmunochemotherapy was associated with on-treatment tumour microenvironment (TME) remodelling, including upregulation of anti-TMEs signatures, downregulation of pro-TMEs signatures, reversing CD8+ T exhaustion, and repolarizing proinflammatory TAMs. For the patients achieving a complete response, the cytotoxic activity of CD8+ T cells was stimulated and more interferon-gamma was provided, which would be the key for TAMs proinflammatory repolarization and eventually promote the CD8+ T cells maturation in turn. Among patients who did not reach complete response, differentiation and hypoxia signatures for endothelial cells were elevated after therapy. These patients exhibited higher levels of immune checkpoint genes in malignant cells at the baseline (before treatment), and decreased tumour antigen presentation activity, which may underlie the resistance mechanism to therapy.ConclusionsThis study pictures a map of TME modulation following immunochemotherapy-based combination induction therapy and provides potential future approaches.HighlightsImmunochemotherapy remodeled T cell phenotypes. For the patients achieving complete response, more interferon gamma was provided by CD8+ T cells after therapy, which would be the key for TAMs pro-inflammatory repolarization and eventually promote the CD8+ T cells maturation in turns. Among patients who did not reach complete response, malignant cells exhibited higher level of immune checkpoint genes before therapy, and decreased tumor antigen presentation activity, which may underlie the resistance mechanism to therapy.

Dataset Information

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

Background

Methods

Results

Conclusions

Publications

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

Similar Datasets

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