Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA556461 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12565234.fastq.gz | Fastqsanger.gz | |||
| SRR12565235.fastq.gz | Fastqsanger.gz | |||
| SRR12565236.fastq.gz | Fastqsanger.gz | |||
| SRR12565237.fastq.gz | Fastqsanger.gz | |||
| SRR12565238.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 163 |
Similar Datasets
Project description:Clinical benefits of cytokine blockade in ileal Crohn’s disease (iCD) are limited to a subset of patients. Here we applied single cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct connectivity network that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in 4 independent iCD cohorts (n=441), and its presence at diagnosis correlated with failure to achieve corticosteroid-free durable remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities
2019-08-29 | GSE134809 | GEO
Project description:Purpose: IBD diagnosis correlation with failure to achieve corticosteroid-free durable remission upon anti-TNF therapy Results: Enrichment of the GIMATS module (unique cellular signature found in a small cohort of surgically resected iCD ileums by scRNAseq) was also present in early stages of disease, prior to any biological therapy Conclusion: Confirmed the presence of the GIMATS module in bulk expression dataset and revealed that the presence of the module at diagnosis is associated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy in a pediatric inception cohort
2019-08-21 | GSE134881 | GEO
Project description:Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy
| PRJNA556684 | ENA
Project description:IL23R signaling dependent genes are significantly upregulated in Crohn’s disease non-responders compared to responders during ongoing anti-TNF therapy
2018-05-01 | GSE111761 | GEO
Project description:Clinical benefits of cytokine blockade in ileal Crohn's disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.
| S-EPMC7060942 | biostudies-literature
Project description:A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor-prognosis wound signature is strongly associated with induction of both a mitochondria gene module and a proteasome gene module. We found that 3-bromopyruvic acid, which inhibits glycolysis, selectively killed breast cells expressing the mitochondria and wound signatures. In addition, inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed breast cells expressing the wound signature. Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies. Cell Line: Transduced construct Computed
2010-06-29 | E-GEOD-8957 | biostudies-arrayexpress
Project description:Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternatively-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balanced of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis and signaling pathway deconvolution. Our findings reveal that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way dependent on JNK signaling. We uncover principles of the selectively inhibition by TNF via the type 1 TNF receptor on specific populations of alternative activated macrophages.
2022-01-07 | PXD028667 | Pride
Project description:A major goal of cancer research is to match specific therapies to molecular targets in cancer. Genome-scale expression profiling has identified new subtypes of cancer based on consistent patterns of variation in gene expression, leading to improved prognostic predictions. However, how these new genetic subtypes of cancers should be treated is unknown. Here we show that a gene module map can guide the prospective identification of targeted therapies for genetic subtypes of cancer. By visualizing genome-scale gene expression in cancer as combinations of activated and deactivated functional modules, gene module maps can reveal specific functional pathways associated with each subtype that might be susceptible to targeted therapies. We show that in human breast cancers, activation of a poor-prognosis wound signature is strongly associated with induction of both a mitochondria gene module and a proteasome gene module. We found that 3-bromopyruvic acid, which inhibits glycolysis, selectively killed breast cells expressing the mitochondria and wound signatures. In addition, inhibition of proteasome activity by bortezomib, a drug approved for human use in multiple myeloma, abrogated wound signature expression and selectively killed breast cells expressing the wound signature. Thus, gene module maps may enable rapid translation of complex genomic signatures in human disease to targeted therapeutic strategies. Cell Line: Transduced construct Keywords: cell_type_comparison_design
2008-01-28 | GSE8957 | GEO
Project description:International guidelines recommend deciding the treatment of colorectal lesions based on the estimated histology by endoscopic optical diagnosis. However, the theoretical and practical knowledge on optical diagnosis is not widely expanded
The mail goal of this randomised controlled trial is to compare the pooled sensitivity of optical diagnosis for predicting deep submucosal invasion in large non-pedunculated polyps > 20 mm assessed in routine colonoscopies of gastroenterologists attending a e-learning module (intervention group) vs gastroenterologists who do not (control group)
The main questions the study aims to answer are:
* Is the pooled sensitivity of optical diagnosis for predicting deep submucosal invasion in large non-pedunculated polyps assessed in routine colonoscopies increased in those gastroenterologists participating in the e-learning module?
* Is the pooled diagnostic accuracy of optical diagnosis for predicting deep sm invasion in large non-pedunculated polyps ≥ 20 mm assessed in routine colonoscopies increased in those gastroenterologists participating in the e-learning module?
* In lesions with submucosal invasion, is the en bloc and complete resection rate (R0) increased in those gastroenterologists participating in the e-learning module?
* In lesions referred to surgery, is the pooled benign polyps rate decreased in those gastroenterologists participating in the e-learning module?
* In lesions treated with advanced en bloc procedures (ESD, TAMIS, fullthickness resection), is the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion increased in those gastroenterologists participating in the e-learning module?
* In lesions treated with piecemeal endoscopic resection, is the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion decreased in those gastroenterologists participating in the e-learning module?
* Is the diagnostic accuracy for predicting deep submucosal invasion in a test with pictures increased after participating in the e-learning module?
The participants (or subjects of study) are gastroenterologists. They will be randomised to do the e-learning course (intervention group) or not (control group).
Researchers will compare clinical outcomes of gastroenterologists participating in the e-learning module vs gastroenterologists not participating in the e-learning module to see if:
* the pooled sensitivity of optical diagnosis for predicting deep submucosal invasion in large non-pedunculated polyps > 20 mm assessed in routine colonoscopies is increased.
* the pooled diagnostic accuracy of optical diagnosis for predicting deep sm invasion in large non-pedunculated polyps > 20 mm is increased.
* the en bloc and complete resection rate (R0) is increased in lesions with submucosal invasion.
* the pooled benign polyps rate decreased in lesions referred to surgery.
* the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion increased in lesions treated with advanced en bloc procedures (ESD, TAMIS, fullthickness resection).
* the pooled rate of histology with high-grade dysplasia, intramucosal cancer or submucosal invasion decreased in lesions treated with piecemeal endoscopic resection.
* the diagnostic accuracy for predicting deep submucosal invasion in a test with pictures after participating is increased.
| 3397 | ecrin-mdr-crc
Project description:Background: Perianal fistulising Crohn’s disease (pfCD) is a disabling phenotype of Crohn’s disease (CD) with suboptimal outcomes. We assessed neutrophil extracellular traps (NETs) in perianal fistulas and implicated their roles in pfCD healing. Methods: Patients with complex pfCD who developed preplaced seton drainage were recruited during the verified maintenance of remission in CD. Fistula tracts were sampled during definitive surgery plus seton removal. Patient demographics, CD classification, medication strategy, and healing of pfCD were recorded. RNA sequencing was applied for transcriptomic profile analysis. NETs components, including myeloperoxidase (MPO), neutrophil elastase (NE), and citrullinated histone H3 (CitH3), were identified using immunofluorescence. Serum infliximab (IFX), anti-IFX antibodies, and tissue levels of IFX, adalimumab (ADA), MPO and CitH3 were determined using enzyme-linked immunosorbent assays. Peptidyl arginine deiminase IV (PAD4), tumour necrosis factor (TNF)-α, and NE were detected using immunohistochemistry. Gene expression levels of PAD family members were assessed with qPCR. Results: Twenty-one patients were included, 15 of whom adopted IFX as maintenance treatment. RNA-seq revealed difference in neutrophil associated pathways between unhealed and healed fistulas. NETs components (MPO/NE/CitH3) were detectable in the fistulas and were parallel with the PAD4 levels. Eleven of 21 (52%) patients experienced complete healing of the pfCD 108 weeks post-operatively. Fistula NETs were significantly increased in patients with unhealed pfCD. Increased NETs were associated with abundant TNF-α production and the absence of IFX in fistulas. Conclusions: NETs exist in pfCD fistulas, which are associated with unhealed post-operative fistulas in pfCD, suggesting their prognostic roles in pfCD.
2023-10-07 | GSE215067 | GEO