Single-cell transcriptomic analysis (scRNA-seq) of healthy adult human parietal pleura
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE243446 | GEO | 2023/09/21
REPOSITORIES: GEO
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Project description:Genome-wide profile of pleural mesothelioma versus parietal and visceral pleura
2009-01-01 | E-MTAB-47 | biostudies-arrayexpress
Project description:Mesothelioma is an incurable, asbestos-exposure related cancer that typically affects the lining or pleura of the lungs. Symptoms typically develop many decades after initial exposure to asbestos, leaving an enduring legacy of disease. Vaccine-induced augmentation of immune responses unleashed during checkpoint blockade may provide further clinical benefit in mesothelioma. In this study we explore the HLA class I antigenic landscape (or immunopeptidome) of mesothelioma in patient derived cell line and clinical material (pleural effusion samples).
2025-05-07 | PXD054498 | Pride
Project description:Malignant mesothelioma is an aggressive tumour arising from the mesothelial cells lining the pleura, peritoneum or pericardium. The principal carcinogen associated with malignant mesothelioma is asbestos . A transgenic mouse model, denoted MexTAg, which encodes the Simian Virus 40 (SV40) large T antigen (TAg) downstream of the mesothelin promoter was developed. Inactivation of the tumour suppressors p53 and RB following binding to TAg results. In this model mesothelioma develops in the mesothelial cell compartment after the mice have been exposed to asbestos. The MexTAg transgenic mouse model of mesothelioma model enables analysis of the molecular events associated with asbestos induced mesothelioma and is utilised here to investigate the molecular dynamics of tumours induced in these mice, using gene expression patterns as a read out.
2016-01-30 | E-MTAB-3988 | biostudies-arrayexpress
Project description:BACKGROUND: Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). MicroRNAs (miRNAs) are small non-coding RNA-strands (~22 nucleotides) that post-transcriptionally regulate gene-expression. Studies have shown that miRNAs are potential diagnostic markers in other cancers; however, it is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMP. OBJECTIVE: To identify differentially expressed microRNAs which can aid in the diagnostics of MPM. METHODS: We screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed paraffin-embedded (FFPE) preoperative diagnostic biopsies, surgically resected MPM-specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP) from 5 patients. RESULTS: By comparing the change in microRNA expression in patient-matched tissue samples, we identify 14 miRNAs which exhibit statistically significant deregulation between sample groups. CONCLUSION: Based on this initial screening of miRNA expression, we have identified 14 miRNAs which are potential diagnostic biomarkers and may aid in diffferentiating RMP from MPM. qPCR microRNA expression profiling. MicroRNA expression in surgical tissue samples and presurgery diagnostic biopsies of malignant pleural mesotheliomas was compared to corresponding patient-matched non-neoplastic pleura. Patient-matched diagnostic biopsies from still chemotherapy-naïve patients were included to test for chemotherapy-induced changes in microRNA expression.
2014-01-25 | E-GEOD-54394 | biostudies-arrayexpress
Project description:Tumor metastasis commonly affects pleura in advanced lung cancer and is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Here, by integrating 180785 single cells from lung cancer and control samples, the most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Four subtypes were divided, including one predominately identified in malignant pleural effusion which was characterized by enriched cancer related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing assay, and EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the increased invasiveness of lung cancer cells induced by mesothelial cells. Moreover, EPGN-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, which may facilitate cancer progression.
2024-06-26 | GSE242951 | GEO
Project description:Exposure to asbestos fibres causes profound pathological changes in the pleural cavity and can result in the development of a fatal tumour, malignant mesothelioma (MM). Due to their structural similarities there is concern that carbon nanotubes (CNTs) may present a similar inhalation hazard. However the underlying mechanisms leading to fibre-mediated mesothelioma development are not yet fully understood. To investigate the molecular changes which occur at the mesothelium as a consequence of direct exposure to fibres, short and long asbestos fibres (SFA and LFA) and short and long CNTs (NTS and NTL) were instilled directly into the pleural cavity in mice. After 12 weeks RNA was extracted from the diaphragm and microarray analysis was performed on all of the treatment groups compared to a 0.5% BSA/saline control. Concurrent histopatholgical investigations were performed and revealed that exposure to fibres resulted in responses that were dependent upon the length of the fibres, but not on fibre type. In response to NTL and LFA there was acute inflammation and fibrosis on the parietal pleura; no inflammatory changes were detected histologically after exposure to SFA and NTS. Furthermore, changes in the mTOR signalling pathway were observed. Thus, this study served to illustrate which pathways are involved in the development of fibre-mediated toxicity, and demonstrated that pleural lesions induced by long asbestos fibres and long CNT exhibit a common pro-oncogenic molecular signature.
2017-11-20 | GSE51636 | GEO
Project description:Introduction: Pleural mesothelioma (PM) is known as one of the most aggressive malignancies among all cancers, despite of usually absent tumor-driver mutations in oncogenes. It develops in a unique inflammatory tumor microenvironment (TME), which has been postulated as major contributor of PM’s highly aggressive nature. Mesothelioma-associated fibroblasts (Meso-CAFs), a main component of the TME have recently been shown to substantially stimulate several aspects of PM aggressiveness and promote the malignant transformation of pleural mesothelial cells. However, respective cell models for TME research in PM are still very limited. The most commonly used pleural mesothelial cell line Met5A has been established decades ago and patient-derived Meso-CAFs have just recently been characterized for the first time. The aim of the current study was to generate and characterize pleural mesothelial and Meso-CAF cell models with an extended life span that closely resemble the primary cells isolated from human tissue. Methods: Pleural mesothelial cells and Meso-CAFs were isolated from human tissue of pneumothorax and PM patients, respectively. Retroviral transduction was used to induce stable expression of human telomerase reverse transcriptase (hTERT) and enhanced green fluorescent protein (EGFP) in the primary cells. The established cell models were evaluated by measuring their doubling times, gene expression and protein activity levels of hTERT, as well as the absolute lengths of telomeres. The transduced cells were compared to their primary counterparts on the protein level using proteome analysis and the impact of their conditioned media (CM) on tumor cell growth was investigated by videomicroscopy. Results: All transduced derivatives exhibit elevated hTERT gene expression and protein activity, increased hTERT protein amounts in the nucleus, and moderately higher absolute telomere lengths compared to their parental primary cells. The transduction with hTERT did not elicit marked changes in the morphology of the cells, as well as in their proteomes and secretomes. The CM of primary and hTERT-transduced Meso-CAFs comparably stimulated PM cell growth, while medium conditioned by normal pleural mesothelial cells including their hTERT-transduced derivatives was not able to induce a growth stimulating effect. Conclusion: The hTERT-transduced cells closely resemble their primary counterparts, while retaining telomerase activity, thus preventing replicative senescence. The new cell models provide valuable tools for the investigation of cellular interactions cellular interactions within the TME of PM and thus may help to identify novel biomarkers for early diagnosis and to develop new therapeutic strategies.
2023-10-24 | PXD043511 | Pride
Project description:Introduction: Pleural mesothelioma (PM) is known as one of the most aggressive malignancies among all cancers, despite of usually absent tumor-driver mutations in oncogenes. It develops in a unique inflammatory tumor microenvironment (TME), which has been postulated as major contributor of PM’s highly aggressive nature. Mesothelioma-associated fibroblasts (Meso-CAFs), a main component of the TME have recently been shown to substantially stimulate several aspects of PM aggressiveness and promote the malignant transformation of pleural mesothelial cells. However, respective cell models for TME research in PM are still very limited. The most commonly used pleural mesothelial cell line Met5A has been established decades ago and patient-derived Meso-CAFs have just recently been characterized for the first time. The aim of the current study was to generate and characterize pleural mesothelial and Meso-CAF cell models with an extended life span that closely resemble the primary cells isolated from human tissue. Methods: Pleural mesothelial cells and Meso-CAFs were isolated from human tissue of pneumothorax and PM patients, respectively. Retroviral transduction was used to induce stable expression of human telomerase reverse transcriptase (hTERT) and enhanced green fluorescent protein (EGFP) in the primary cells. The established cell models were evaluated by measuring their doubling times, gene expression and protein activity levels of hTERT, as well as the absolute lengths of telomeres. The transduced cells were compared to their primary counterparts on the protein level using proteome analysis and the impact of their conditioned media (CM) on tumor cell growth was investigated by videomicroscopy. Results: All transduced derivatives exhibit elevated hTERT gene expression and protein activity, increased hTERT protein amounts in the nucleus, and moderately higher absolute telomere lengths compared to their parental primary cells. The transduction with hTERT did not elicit marked changes in the morphology of the cells, as well as in their proteomes and secretomes. The CM of primary and hTERT-transduced Meso-CAFs comparably stimulated PM cell growth, while medium conditioned by normal pleural mesothelial cells including their hTERT-transduced derivatives was not able to induce a growth stimulating effect. Conclusion: The hTERT-transduced cells closely resemble their primary counterparts, while retaining telomerase activity, thus preventing replicative senescence. The new cell models provide valuable tools for the investigation of cellular interactions cellular interactions within the TME of PM and thus may help to identify novel biomarkers for early diagnosis and to develop new therapeutic strategies.
2023-10-24 | PXD043534 | Pride
Project description:EPIC methylation data of pleural mesothelioma samples and healthy pleura samples
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Project description:EPIC methylation data of pleural mesothelioma samples and healthy pleura samples
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