Time-series single-cell RNA sequencing analysis of WT or CCR2-/- murine lungs in silica-induced pulmonary fibrosis model.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA766661 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16089513_1.fastq.gz | Fastqsanger.gz | |||
| SRR16089513_2.fastq.gz | Fastqsanger.gz | |||
| SRR16089514_1.fastq.gz | Fastqsanger.gz | |||
| SRR16089514_2.fastq.gz | Fastqsanger.gz | |||
| SRR16089515_1.fastq.gz | Fastqsanger.gz |
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Project description:microRNAs (miRNAs) play a critical biological role in a variety of pathophysiological processes by suppressing their target genes. However, little is known on the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. To investigate miRNAs of interest in regulation of pulmonary fibrosis, total RNA was isolated from mice lungs collected at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure. Then, miRNA microarray was performed with one mouse lung at each time point. miRNA microarray was performed with one mouse lung at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure to investigate the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. Mouse lung tissues were selected at each time point after treatment for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of lungs at each fibrotic stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected lung tissues according to morphological criteria at five time-points: before silica exposure, i.e. day 0 (D0), the early inflammation phase day 3 (D3) and day 7 (D7), the late inflammation phase, day 14 (D14), the fibrosis phase,i.e. day 28 (D28) and day (D56).
2014-01-29 | E-GEOD-54463 | biostudies-arrayexpress
Project description:A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatic analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top-ranking biological functions perturbed by silica exposure in the A549 cells and rat lungs. The involvement of oxidative stress and apoptosis in the silica-induced pulmonary toxicity was confirmed by ELISA and confocal microscopy analysis, respectively, of the silica-exposed A549 cells. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study, may result in a better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure.
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Project description:microRNAs (miRNAs) play a critical biological role in a variety of pathophysiological processes by suppressing their target genes. However, little is known on the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. To investigate miRNAs of interest in regulation of pulmonary fibrosis, total RNA was isolated from mice lungs collected at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure. Then, miRNA microarray was performed with one mouse lung at each time point. miRNA microarray was performed with one mouse lung at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure to investigate the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis.
2014-01-29 | GSE54463 | GEO
Project description:A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatic analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top-ranking biological functions perturbed by silica exposure in the A549 cells and rat lungs. The involvement of oxidative stress and apoptosis in the silica-induced pulmonary toxicity was confirmed by ELISA and confocal microscopy analysis, respectively, of the silica-exposed A549 cells. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study, may result in a better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. 20 samples were analyzed in this experiment. RNA from rat lung samples was isolated for gene expression studies. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) or air. Lung gene expression profiling was performed using rat lung samples, 8 for silica exposed and 12 for air-exposed controls at 0 weeks post-exposure time period.
2012-06-29 | E-GEOD-30178 | biostudies-arrayexpress
Project description:Non-invasive or minimally invasive surrogate approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. Presently, using a rat model, we have investigated the potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity. Rats were exposed by inhalation to crystalline silica for one week (15 mg/m3, 6-hours/day, 5 days/week). Pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined in the control and silica exposed rats at 32-weeks following termination of silica exposure. A significant elevation in bronchoalveolar lavage fluid (BALF) lactate dehydrogenase (LDH) activity and moderate histological changes in the lungs, including type II pneumocyte hyperplasia and fibrosis, indicated silica-induced pulmonary toxicity in the rats. Similarly, significant infiltration of neutrophils and elevated monocyte chemotactic protein-1 (MCP1) level in the lungs suggested silica-induced pulmonary inflammation in the rats. Microarray analysis of global gene expression profiles identified significant differential expression (>1.5 fold change and FDR p<0.01) of 520 and 537 genes, respectively, in the lungs and blood of the silica exposed rats. Bioinformatics analysis of the differentially expressed genes demonstrated significant similarity in the biological processes, molecular networks, and canonical pathways enriched by silica exposure in the lungs and blood of the rats. Several genes involved in functions relevant to silica-induced pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular movement, fibrosis, etc, were found significantly differentially expressed in the lungs and blood of the silica exposed rats. The results of this study, in addition to providing molecular insights into the mechanisms underlying silica-induced pulmonary toxicity, suggested the potential application of peripheral blood gene expression profiling as a toxicologically relevant and minimally invasive surrogate approach to study the mechanisms underlying silica-induced pulmonary toxicity. Non-invasive or minimally invasive surrogate approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. Presently, using a rat model, we have investigated the potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity. Rats were exposed by inhalation to crystalline silica for one week (15 mg/m3, 6-hours/day, 5 days/week). Pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined in the control and silica exposed rats at 32-weeks following termination of silica exposure. A significant elevation in bronchoalveolar lavage fluid (BALF) lactate dehydrogenase (LDH) activity and moderate histological changes in the lungs, including type II pneumocyte hyperplasia and fibrosis, indicated silica-induced pulmonary toxicity in the rats. Similarly, significant infiltration of neutrophils and elevated monocyte chemotactic protein-1 (MCP1) level in the lungs suggested silica-induced pulmonary inflammation in the rats. Microarray analysis of global gene expression profiles identified significant differential expression (>1.5 fold change and FDR p<0.01) of 520 and 537 genes, respectively, in the lungs and blood of the silica exposed rats. Bioinformatics analysis of the differentially expressed genes demonstrated significant similarity in the biological processes, molecular networks, and canonical pathways enriched by silica exposure in the lungs and blood of the rats. Several genes involved in functions relevant to silica-induced pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular movement, fibrosis, etc, were found significantly differentially expressed in the lungs and blood of the silica exposed rats. The results of this study, in addition to providing molecular insights into the mechanisms underlying silica-induced pulmonary toxicity, suggested the potential application of peripheral blood gene expression profiling as a toxicologically relevant and minimally invasive surrogate approach to study the mechanisms underlying silica-induced pulmonary toxicity.
2012-12-31 | GSE36208 | GEO
Project description:The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.
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Project description:The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.
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Project description:This SuperSeries is composed of the following subset Series: GSE30178: Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling (rat lungs) GSE30180: Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling (A549 cells dataset 1) GSE30200: Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling (A549 cells dataset 2) GSE30213: Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling (A549 cells dataset 3) GSE30214: Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling (A549 cells dataset 4) GSE30215: Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling (A549 cells dataset 5) Refer to individual Series
2012-06-29 | E-GEOD-30216 | biostudies-arrayexpress