Single-cell analysis reveals the immune landscape of benzene-exposed patients and a distinct FCGR3B+ monocyte population
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE309247 | GEO | 2025/10/01
REPOSITORIES: GEO
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Project description:Benzene is a ubiquitous environmental pollutant and an established human hematotoxicant and leukemogen. New insights into the pathogenesis of benzene hematotoxicity are urgently needed. Long non-coding RNA（lncRNA）can regulate gene expression and widely participate in the various physiological and pathological processes. Microarray analysis was used to identify the differentially expressed lncRNA and mRNA that were likely to be critical for benzene hematotoxicity. An integrated analysis of lncRNA and mRNA expression profiles was performed to identify key hub genes, pathways and biological processes. Peripheral blood samples were randomly obtained from four patients of chronic benzene poisoning, three benzene-exposed workers and three health controls without benzene exposure. The occupational history, age, gender, lifestyle such as smoking, drinking, recent drug use situation and medical history in each group were matched. Total RNA was extracted and an integrated analysis of lncRNA and mRNA expression profiles was performed by GeneChip Human Gene 2.0 ST Array (Affymetrix).
2015-07-27 | E-GEOD-50737 | biostudies-arrayexpress
Project description:The effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression was examined in a population of shoe-factory workers with well-characterized occupational exposures to benzene. We compared data from two microarray platforms (Illumina and Affymetrix). Keywords: occupational exposure
2009-05-11 | GSE9569 | GEO
Project description:Benzene is a toxic environmental pollutant that can disrupt the immune system of the human body. Benzene exposure has been reported to reduce immune cells in multiple immune organs. This study used quantitative proteomics to depict benzene-induced spleen injury.
2023-02-08 | PXD039948 |
Project description:Benzene is abundant air pollutant that has been associated with several diseases in particularly cardiovascular disease. Despite of known health risks, effects of benzene on cardiovascular health is not well studied. In this study, in a well-controlled animal model, we are characterizing how benzene influences cardiovascular system.
2023-06-23 | GSE153151 | GEO
Project description:Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational exposure to a range of benzene levels perturbed gene expression in peripheral blood mononuclear cells. In the current study, we sought to identify gene expression biomarkers predictive of benzene exposure below 1 part per million (ppm), the occupational standard in the U.S. First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to benzene (<1 to ≥5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm benzene exposure, in 44 subjects with a mean air benzene level of 0.55±0.248 ppm (minimum 0.203ppm). nCounter and microarray expression levels were highly correlated (coefficients >0.7, p<0.05) for 26 microarray-selected genes. nCounter and mRNA-Seq levels were poorly correlated for 4 mRNA-Seq-selected genes. Using negative binomial regression with adjustment for covariates and multiple testing, we confirmed differential expression of 23 microarray-selected genes in the entire benzene-exposed group, and 27 genes in the <1 ppm-exposed subgroup, compared with the control group. Using SL, we identified 3 pairs of genes that could predict <1 ppm benzene exposure with cross-validated AUC estimates >0.9 (p<0.0001) and were not predictive of other exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses. Using nCounter and SL, we validated the altered expression of multiple mRNAs by benzene and identified gene pairs predictive of exposure to benzene at levels below the US occupational standard of 1ppm.
2018-09-06 | GSE119533 | GEO
Project description:Benzene is a ubiquitous environmental pollutant abundant in household products, petrochemicals and cigarette smoke. Benzene is a well-known carcinogen in humans and experimental animals; however, little is known about the cardiovascular toxicity of benzene. Recent population-based studies indicate that benzene exposure is associated with an increased risk for heart failure. Nonetheless, it is unclear whether benzene exposure is sufficient to induce and/or exacerbate heart failure. We examined the effects of benzene (50 ppm, 6 h/day, 5 days/week, 6 weeks) or HEPA-filtered air exposure on transverse aortic constriction (TAC)-induced pressure overload in male C57BL/6J mice. Our data show that benzene exposure had no effect on cardiac function in the Sham group; however, it significantly compromised cardiac function as depicted by a significant decrease in fractional shortening and ejection fraction, as compared with TAC/Air-exposed mice. RNA-seq analysis of the cardiac tissue from the TAC/benzene-exposed mice showed a significant increase in several genes associated with adhesion molecules, cell-cell adhesion, inflammation, and stress response. In particular, neutrophils were implicated in our unbiased analyzes. Indeed, immunofluorescence studies showed that TAC/benzene exposure promotes infiltration of CD11b+/S100A8+/myeloperoxidase+-positive neutrophils in the hearts by 3-fold. In vitro, the benzene metabolites, hydroquinone and catechol, induced the expression of P-selectin in cardiac microvascular endothelial cells by 5-fold and increased the adhesion of neutrophils to these endothelial cells by 1.5-2.0-fold. Benzene metabolite-induced adhesion of neutrophils to the endothelial cells was attenuated by anti-P-selectin antibody. Together, these data suggest that benzene exacerbates heart failure by promoting endothelial activation and neutrophil recruitment.
2021-12-30 | GSE192643 | GEO
Project description:Human toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks. Key words: occupational exposure
2011-05-14 | GSE21862 | GEO
Project description:Human toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks. Key words: occupational exposure 29 workers exposed to <<1ppm benzene at most dosimetry reading over a 14-month period (Very Low), 30 exposed to average <1ppm (Low), 11 exposed to 5-10 ppm (High), 13 exposed to >10 ppm (Very High), and 42 unexposed controls (Control) who were frequency-matched to these subjects on the basis of age and gender were analyzed (technical replicates on some subjects, see SubjectID/description).
2011-05-14 | E-GEOD-21862 | biostudies-arrayexpress
Project description:There is increasing concern regarding the adverse effects of air pollution on human health, and benzene is a major toxic compound in air pollution. Maternal benzene exposure has been associated with reproductive complications, such as preterm birth, low birth weight, and immunological and neurological complications in the offspring. However, it is poorly understood how benzene induces these complications. Our objective was to establish a full body inhalation mouse model for maternal benzene exposure that mimics clinical phenotypes observed in human populations, and characterize the maternal immune activation and placental response in our model. Here, we report that maternal immune activation triggered by benzene exposure during pregnancy leads to increased resorptions, abnormal placenta development and low birth weight of fetus. More importantly, there is a sexual dimorphic response to benzene exposure in female and male placentas. In the male placenta, the transcriptome changes reveal a more immunologically relevant profile, while females have a metabolically related profile. Furthermore, we discover the sexual dimorphic response could be a consequence of the sexual dimorphism of placenta at baseline, which indicates the significant difference between sexes in terms of the immunological processes in the placenta, both in human and mouse. Therefore, our findings established a benzene exposure mouse model and indicated the sexual dimorphism of placenta, which provides valuable reference for the future pregnancy studies.
2023-07-20 | PXD035085 | Pride
Project description:Benzene is a ubiquitous environmental pollutant and an established human hematotoxicant and leukemogen. New insights into the pathogenesis of benzene hematotoxicity are urgently needed. Long non-coding RNA（lncRNA）can regulate gene expression and widely participate in the various physiological and pathological processes. Microarray analysis was used to identify the differentially expressed lncRNA and mRNA that were likely to be critical for benzene hematotoxicity. An integrated analysis of lncRNA and mRNA expression profiles was performed to identify key hub genes, pathways and biological processes.
2015-07-27 | GSE50737 | GEO