An Integrated Multi-Omics Profiling Landscape of Organizing Pneumonia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Hongmei Wang
PROVIDER: PXD049166 | iProX | Mon Feb 05 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis. Comprehensive multi-omics profiling approaches, including single-cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages. The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis. CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti-ferroptosis and anti-fibrosis effect of CD36 mediated, at least in part, by ceramides. Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.
| S-EPMC11290555 | biostudies-literature
Project description:Cellular senescence is a complex multifactorial biological phenomenon that plays essential roles in aging, and aging-related diseases. During this process, the senescent cells undergo gene expression altering and chromatin structure remodeling. However, studies on the epigenetic landscape of senescence using integrated multi-omics approaches are limited. In this research, we performed ATAC-seq, RNA-seq and ChIP-seq on different senescent types to reveal the landscape of senescence and identify the prime regulatory elements. We also obtained 34 key genes and deduced that NAT1, PBX1 and RRM2, which interacted with each other, could be the potential markers of aging and aging-related diseases. In summary, our work provides the landscape to study accessibility dynamics and transcriptional regulations in cellular senescence. The application of this technique in different types of senescence allows us to identify the regulatory elements responsible for the substantial regulation of transcription, providing the insights into molecular mechanisms of senescence.
| S-EPMC9638896 | biostudies-literature
Project description:Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to We performed single-cell transcriptomic and proteomic profiling of aortic lesions and peripheral blood samples, respectively, from patients with AD and healthy subjects. We then integrated single-cell RNA to identify phenotype-relevant subpopulations.
2024-11-01 | GSE254132 | GEO
Project description:Cellular senescence is a complex multifactorial biological phenomenon that plays essential roles in aging, and aging-related diseases. During this process, the senescent cells undergo gene expression altering and chromatin structure remodeling. However, studies on the epigenetic landscape of senescence using integrated multi-omics approaches are limited. In this research, we performed ATAC-seq, RNA-seq, and ChIP-seq on different senescent types to reveal the landscape of senescence and identify the prime regulatory elements.
2022-08-15 | GSE210285 | GEO
Project description:Epithelial ovarian cancer has a low response rate to immunotherapy and a complex immune microenvironment that regulates its treatment outcomes. Understanding the immune microenvironment and its molecular basis is of great clinical significance in the effort to improve immunotherapy response and outcomes. To determine the characteristics of the immune microenvironment in ovarian cancer, we stratified ovarian cancer patients into three immune subtypes (C1, C2, and C3) using immune-related genes based on gene expression data from The Cancer Genome Atlas and found that these three subtypes had significant differences in immune characteristics and prognosis. Methylation and copy number variant analysis showed that the immune checkpoint genes that influenced immune response were significantly hypermethylated and highly deleted in the immunosuppressive C3 subtype, suggesting that epigenetic therapy may be able to reverse the efficacy of immunotherapy. In addition, the mutation frequencies of BRCA2 and CDK12 were significantly higher in the C2 subtype than in the other two subtypes, suggesting that mutation of DNA repair-related genes significantly affects the prognosis of ovarian cancer patients. Our study further elucidated the molecular characteristics of the immune microenvironment of ovarian cancer, which providing an effective hierarchical method for the immunotherapy of ovarian cancer patients, and has clinical relevance to the design of new immunotherapies and a reasonable combination strategies.
| S-EPMC8247482 | biostudies-literature
Project description:Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and also cause chronic infections commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we profiled performed to assay for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To find the pivotal transcription factors that are likely involved in host immune defense, we integrally investigated systematic changes in chromatin accessibility and gene expression in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics studies. We discovered that Stat1 and Stat3 were altered in various omics and found similar results in mouse alveolar macrophages. Taken together, these findings indicate that these crucial transcription factors and their downstream signaling molecules play a critical role in the mobilization of host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, as well as provide clear insights and resources for using integrative histological analyses.
2023-07-27 | GSE233206 | GEO
Project description:Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to streamline the identification of individuals at elevated risk for postoperative AAEs, and therapeutic targets to optimize the efficacy of TEVAR for patients with AD. Here, we perform proteomic and single-cell transcriptomic analyses of peripheral blood and aortic lesions, respectively, from patients with AD and healthy subjects. The integrated multi-omics profiling identifies that highly phenotype-associated macrophages orchestrate neutrophil extracellular traps (NETs) through CXCL3/CXCR2 axis, thereby promoting the development of AD. Increased NETs formation is a defining feature of systemic immunity and aortic microenvironment of AD. Inhibiting NETs formation through the blockade of citrullinated histone H3 or CXCL3/CXCR2 axis ameliorates the progression and rupture of aortic dissection in male mice. The plasma level of citrullinated histone H3 predicts AAEs following endovascular therapy, facilitating the risk stratification and prognostic evaluation for patients with AD.
| S-EPMC11686284 | biostudies-literature
Project description:Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and also cause chronic infections commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we profiled performed to assay for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To find the pivotal transcription factors that are likely involved in host immune defense, we integrally investigated systematic changes in chromatin accessibility and gene expression in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics studies. We discovered that Stat1 and Stat3 were altered in various omics and found similar results in mouse alveolar macrophages. Taken together, these findings indicate that these crucial transcription factors and their downstream signaling molecules play a critical role in the mobilization of host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, as well as provide clear insights and resources for using integrative histological analyses.
2023-07-27 | PXD038001 | Pride
Project description:Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and also cause chronic infections commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we profiled performed to assay for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To find the pivotal transcription factors that are likely involved in host immune defense, we integrally investigated systematic changes in chromatin accessibility and gene expression in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics studies. We discovered that Stat1 and Stat3 were altered in various omics and found similar results in mouse alveolar macrophages. Taken together, these findings indicate that these crucial transcription factors and their downstream signaling molecules play a critical role in the mobilization of host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, as well as provide clear insights and resources for using integrative histological analyses.
2023-07-27 | PXD042381 | Pride
Project description:Inhibiting STAT3 signaling reduces tumor progression, metastases and chemoresistance, however the precise molecular mechanism has not been fully delineated in ovarian cancer. Methods: In this study, we generated STAT3 knockout (KO) ovarian cancer cell lines. Effect of STAT3 KO on cell proliferation, migration and spheroid formation was assessed in vitro and effect on in vivo tumor growth was tested using several tumor xenograft models. We used multi-omic genome-wide profiling to identify multi-level (Bru-Seq, RNA-Seq, and MS Proteomic) expression signatures of STAT3 KO ovarian cancer cells.
2019-07-17 | GSE134375 | GEO