CD8 T-cells from pSS patients and human healthy volunteers
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE93683 | GEO | 2017/05/19
SECONDARY ACCESSION(S): PRJNA361556
REPOSITORIES: GEO
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Project description:Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.
2017-05-19 | GSE94510 | GEO
Project description:Multi-omics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology. We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation. Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 T cells were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS. Our multi-omics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level. Proteomics and FACS data will be found in Synapse. https://www.synapse.org/#!Synapse:syn8483276
2017-05-19 | GSE84844 | GEO
Project description:Transcriptome analysis of submandibular glands in female MyD88+/+ and MyD88−/− NOD mice. Sjögren's syndrome (SS) is an autoimmune disease characterized by dysfunction of salivary glands (SGs) and lacrimal glands, which is caused by chronic inflammation associated with autoantibody and autoreactive lymphocyte infiltration. The pathogenic mechanism of SS has not been fully elucidated. Infiltrated lymphocytes form regularized structures similar to lymphoid follicles of secondary lymphoid organs, such as T/B cell compartments, high endothelial venules (HEVs), lymphatic vessels, and germinal centers, therefore being believed as an ectopic lymphoid tissue called tertiary lymphoid organs (TLO). We previously found that deletion of the Toll-like receptor/IL-1 receptor (TLR/IL-1R) adaptor molecule gene Myd88 in SS model mice NOD reduced the frequency of lymphocyte infiltration and HEV formation in SGs. In this study, we analyzed the effect of MyD88 deficiency on lymphoid follicle formation in SGs of NOD mice. Microarray analysis showed decreased expression of genes related to TLO, such as Cxcl13 and Cxcr5, in Myd88-deficient SGs. These results indicate that deficiency of TLR/IL-1R signaling decrease gene expression ot chemokines in SGs, suggesting MyD88-dependent signaling is directly involved in formation of lymphoid follicles in SS.
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Project description:While all salivary glands (SGs) can be involved in primary Sjögren’s syndrome (pSS), their respective role in pathogenesis remains unclear. To assess immunopathway activation in paired parotid and labial gland tissue from biopsy-positive and biopsy-negative pSS and non-SS sicca patients, paraffin-embedded, paired parotid and labial salivary gland tissue and peripheral blood mononuclear cells were obtained from 39 pSS and 20 non-SS sicca patients. The patients were subdivided based on fulfillment of ACR-EULAR criteria and histopathology and the samples were analyzed for differentially expressed genes (DEGs). The principal component analysis of SG gene expression could only separate biopsy-positive pSS from non-SS sicca patients. However, when comparing the transcriptome of biopsy-positive pSS and biopsy-negative non-SS sicca patients, 1235 and 624 DEGs (FDR<-1 or >1) were identified for parotid and labial glands, respectively. The number of DEGs between biopsy negative pSS and non-SS sicca patients was scarce. The overall, transcript expression levels correlated strongly between parotid and labial glands (R2=0.86, p‐value<0.0001). Gene signatures present in both glands of biopsy‐positive pSS patients included IFN‐α signaling, IL-12/IL-18 signaling, CD3/CD28 T-cell activation, CD40 signaling in B-cells, DN2 B-cells, and FcRL4+ B-cells. Signature scores varied considerably amongst pSS patients. In conclusion, the transcriptomes of paired major and minor SGs in pSS were overall comparable, although significant inter-individual heterogeneity in immunopathway activation existed. The SG transcriptome of biopsy-negative pSS was indistinguishable from non-SS sicca patients. The different patterns of SG immunopathway activation in pSS argue for personalized treatment approaches.
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Project description:While all salivary glands (SGs) can be involved in primary Sjögren’s syndrome (pSS), their respective role in pathogenesis remains unclear. To assess immunopathway activation in paired parotid and labial gland tissue from biopsy-positive and biopsy-negative pSS and non-SS sicca patients, paraffin-embedded, paired parotid and labial salivary gland tissue and peripheral blood mononuclear cells were obtained from 39 pSS and 20 non-SS sicca patients. The patients were subdivided based on fulfillment of ACR-EULAR criteria and histopathology and the samples were analyzed for differentially expressed genes (DEGs). The principal component analysis of SG gene expression could only separate biopsy-positive pSS from non-SS sicca patients. However, when comparing the transcriptome of biopsy-positive pSS and biopsy-negative non-SS sicca patients, 1235 and 624 DEGs (FDR<-1 or >1) were identified for parotid and labial glands, respectively. The number of DEGs between biopsy negative pSS and non-SS sicca patients was scarce. The overall, transcript expression levels correlated strongly between parotid and labial glands (R2=0.86, p‐value<0.0001). Gene signatures present in both glands of biopsy‐positive pSS patients included IFN‐α signaling, IL-12/IL-18 signaling, CD3/CD28 T-cell activation, CD40 signaling in B-cells, DN2 B-cells, and FcRL4+ B-cells. Signature scores varied considerably amongst pSS patients. In conclusion, the transcriptomes of paired major and minor SGs in pSS were overall comparable, although significant inter-individual heterogeneity in immunopathway activation existed. The SG transcriptome of biopsy-negative pSS was indistinguishable from non-SS sicca patients. The different patterns of SG immunopathway activation in pSS argue for personalized treatment approaches.
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Project description:Studies on aging have largely included one or two OMICS layers, which may not necessarily reflect the signatures of other layers. Moreover, most aging studies have often compared very young (4-5 wks) mice with old (24 months) mice which does not reflect the aging transition after the attainment of adulthood. Therefore, we aimed to study and compared muti-OMICS aging signatures across key metabolic tissues of mature adults (6 months) and old (24 months) C57BL/6J mice (the most commonly used mouse strain). We compared the differentially regulated genes and enriched pathways for transcriptome, proteome and epigenome (H3K27ac, H3K4me3, H3K27me3, DNA methylation) across different tissues. Here are transcriptome data from Affymatrix microarrays.
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Project description:Background: Synovial sarcoma (SS) occur in children as well as in adults, although metastatic events are much more common in the latter. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC) and genomic (GI) prognostic signatures related to chromosome integrity in sarcomas and gastrointestinal stromal tumors (GISTs). Here we investigate whether these signatures can also predict outcomes in SS. Methods: One hundred primary untreated SS were selected for expression and genomic profiling in a training/validation approach. Results: CINSARC and GI have strong, independent and validated prognostic values (p<0.0001). Comparing expression profiles of tumors with or without metastasis, 14 genes common with the CINSARC signature were identified and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult vs. pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis. Conclusions: Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and GI are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. GI is potentially the best overall biomarker, and clearly the most clinically relevant, considering that genome profiling from formalin fixed samples is already used in pathology. 34 Synovial Sarcomas hybridized to Agilent-026652 Whole Human Genome Microarray 4x44K
2014-08-09 | E-GEOD-40018 | biostudies-arrayexpress
Project description:Background: Synovial sarcoma (SS) occur in children as well as in adults, although metastatic events are much more common in the latter. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC) and genomic (GI) prognostic signatures related to chromosome integrity in sarcomas and gastrointestinal stromal tumors (GISTs). Here we investigate whether these signatures can also predict outcomes in SS. Methods: One hundred primary untreated SS were selected for expression and genomic profiling in a training/validation approach. Results: CINSARC and GI have strong, independent and validated prognostic values (p<0.0001). Comparing expression profiles of tumors with or without metastasis, 14 genes common with the CINSARC signature were identified and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult vs. pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis. Conclusions: Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and GI are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. GI is potentially the best overall biomarker, and clearly the most clinically relevant, considering that genome profiling from formalin fixed samples is already used in pathology. 58 Synovial Sarcomas hybridized to Agilent-014850 Whole Human Genome Microarray 4x44K G4112F
2014-08-09 | E-GEOD-40021 | biostudies-arrayexpress
Project description:Background: Synovial sarcoma (SS) occur in children as well as in adults, although metastatic events are much more common in the latter. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC) and genomic (GI) prognostic signatures related to chromosome integrity in sarcomas and gastrointestinal stromal tumors (GISTs). Here we investigate whether these signatures can also predict outcomes in SS. Methods: One hundred primary untreated SS were selected for expression and genomic profiling in a training/validation approach. Results: CINSARC and GI have strong, independent and validated prognostic values (p<0.0001). Comparing expression profiles of tumors with or without metastasis, 14 genes common with the CINSARC signature were identified and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult vs. pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis. Conclusions: Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and GI are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. GI is potentially the best overall biomarker, and clearly the most clinically relevant, considering that genome profiling from formalin fixed samples is already used in pathology.
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