Population RNA Seq of enriched human peripheral blood monocytes treated with at-RA/4-oxo-RA/DMSO for 24h in culture
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Homo sapiens
SUBMITTER:
PROVIDER: E-MTAB-14660 | biostudies-arrayexpress |
SECONDARY ACCESSION(S): ERP166719
REPOSITORIES: biostudies-arrayexpress
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2025-02-06 | E-MTAB-13505 | biostudies-arrayexpress
Project description:Study of the effects of at-RA treatment on the transcriptome of murine Long-Term Hematopoietic Stem Cells (LT-HSCs) in the context of myocardial infarction (MI). MI was induced in female C57BL/6J mice aged 6 to approximately 12 weeks through permanent occlusion of the left anterior descending artery (LAD). Mice were intraperitoneally injected on the 1st and 2nd day after MI surgery with either 30 mg/kg body weight at-RA (Sigma-Aldrich; MI+at-RA condition), or with the corresponding amount of DMSO in phosphate-buffered saline (PBS) (MI+vehicle condition). Two days after MI, LT-HSCs (Lin-negative, Sca1-positive, c-Kit-positive, CD150-positive, CD48-negative, CD34-negative) were isolated from the bone marrow, sorted, and analyzed for their transcriptome profiles. This study aimed to understand how at-RA treatment influences gene expression in LT-HSCs following MI.
2025-02-06 | E-MTAB-13506 | biostudies-arrayexpress
Project description:An exploration of the peripheral blood CD4+ T-cell transcriptome of early arthritis clinic attendees, seeking novel diagnostic tools and pathophysiological insights. Ex-vivo CD4+ T-cell RNA was obtained following first early arthritis clinic attendance from 173 patients. Four diagnostic categories were confirmed at median 28 months follow-up. Outcome categories are ACPA- RA (A; n=31), ACPA+ RA (B; n=41), Non-RA Inflammatory arthritis (C; n=56), and Non-RA/Non-Inflammatory arthritis (D; n=45). In order to derive and validate a diagnostic gene signature, samples were split into Training set (where patients could be diagnosed at presentation; n=111) and validation set of undifferentiated arthritis (UA; n=62) patients, in whom diagnosis could only be confirmed after the follow-up period. Arrays were processed in two phases (phases 1 and 2). Phase 1 was split into 4 labelling batches, Phase 2 was split into 2 labelling batches. Batch effects were controlled for using this information using the empirical Bayes approach of Johnson et al. (2007). The supplementary file 'GSE20098_non-normalized.txt' contains non-normalized data for Samples GSM502124-GSM502280 and GSM506251-GSM506266.
2012-03-03 | E-GEOD-20098 | biostudies-arrayexpress
Project description:Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention. Expression profiles of human peripheral blood monocytes activated in vivo and stimulated in vitro. Monocytes from patients with SLE and RA and from healthy donors were used for generating disease-specific gene-expression profiles, where these profiles represent in vivo activation of monocytes. In addition, monocytes from healthy donors were stimulated in vitro by cytokines: TNFα, IFNα2a and IFNγ. Cytokine-specific gene-expression profiles were generated by comparing stimulated monocytes with unstimulated ones. TNFα-, IFNα2a- and IFNγ as cytokine-specific gene-expression profiles were compared with RA and SLE, as disease-specific gene-expression profiles.
2012-06-13 | E-GEOD-38351 | biostudies-arrayexpress
Project description:All the synovial tissue specimens for TMT relative quantitative proteomics and further experiments were obtained from the patients with RA or OA undergoing surgical joint replacement at the clinical of joint surgery (Xi'an Hong Hui Hospital, Xi'an Jiaotong University, China). The diagnosis of the patients were accorded to the criteria of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) in 2010.a quantitative proteomic profiling of synovial tissue obtained from RA and OA patients was carried out by using TMT labeling followed by high resolution mass spectrometry analysis. We have identified 4822 proteins out of which 510 proteins were found to be differentially expressed by ≥1.2 fold change in the synovial tissue from RA verses OA patients.
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Project description:Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLS) and synovial macrophages (SM), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLS of RA patients (RA-FLS) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone, although it remains unresolved how RA-FLS exhibit invasive phenotype. RA-FLS and SM originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. Presently, we performed global transcriptome profiling of FLS and SM obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLS and pro-inflammatory properties of RA synovial macrophages (RA-SM), respectively. Interestingly, under interleukin1β-stimulated condition, RA-FLS newly acquired pro-inflammatory signature mimicking RA-SM without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including POSTN and TWIST1, as novel regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLS and were further instigated by interleukin1β. In vitro functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLS stimulated with interleukin1β. Taken together, our systems approach to rheumatoid synovitis provides a basis for identifying novel regulators responsible for pathological features of RA-FLS and RA-SM, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. To identify molecular signatures of FLS and MLS in RA joints, we isolated FLS from synovial tissues of RA and osteoarthritis (OA) patients, obtained synovial macrophages from synovial fluid of RA patients, and differentiated control macrophages from peripheral blood of healthy subjects. Also, we stimulated FLS with IL1β, and then analyzed gene expression profiles of both IL1β-stimulated RA-FLS and OA-FLS
2014-01-09 | E-GEOD-49604 | biostudies-arrayexpress
Project description:Background: Rheumatoid arthritis (RA) is a complex heterogenous autoimmune disease and achieving long term disease remission is an elusive goal for patients, thus implying improvement in drug targeting is necessary. Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in RA. Therefore, oral inhibitors of specific kinases, such as Cyclin Dependent Kinases (CDKs) and Janus Kinase (JAKs), are under development or have been approved. However, the cell signalling mechanisms in treatment naïve RA patients is yet to be explored, which may facilitate targeted therapy stratification. Methods: We undertook phosphoproteome and total proteome analysis of 8 pre-treatment synovial biopsies of RA patients using label-free mass spectrometry. Results: The analysis revealed a clear separation of the phosphoproteome and proteome profile between the lymphoid and myeloid RA pathotypes. Differential expression analysis and function enrichment showed that the degree of inflammatory state and specific signalling activities are associated with different RA pathotypes. The lymphoid pathotype was enriched with immunological pathways and associated with Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted kinases not previously linked to RA, such as Serine/Threonine Protein Kinase N1 (PKN1) in the lymphoid pathotype and Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotypes. Certain phosphosites were also highly correlated with clinical features, such as Disabled Homolog 2 (DAB2)-Ser723 with Disease Activity Score (DAS)-28, and so these may be potential biomarkers of disease progression and response. Conclusions: These data provide evidence that specific phosphoproteome and proteome signatures are associated with different RA pathotypes and may have clinical utility for stratifying patients as part of a personalised medicine approach.
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Project description:Retinoid homeostasis is critical for normal embryonic development, and both the deficiency and excess of these compounds are associated with congenital malformations. Here we found that SIRT1, the most conserved mammalian NAD+-dependent deacetylase, contributes to the maintenance of homeostatic retinoic acid (RA) signaling and modulates mouse embryonic stem cell (mESC) differentiation. Our data show that SIRT1 deficiency enhances RA signaling, thereby accelerating mES cell differentiation in response to RA. Our findings highlight the importance of SIRT1 in transcriptional regulation of ESC pluripotency and embryogenesis. Three pairs of sh-Control and sh-SIRT1 E14 mESC cells (with dulpicate for each sample) were treated with vehicle ethanol or with 20 nM of RA for 2 days. Total RNA was isolated using a Qiagen RNA easy mini kit with on-column DNAseI treatment. RNA quality was validated with the Agilent 2100 Bioanalyzer in the microarray facility. Three-pairs of ethanol treated samples, and 4 RA treated sh-Control, and 6 RA treated sh-SIRT1 samples were analyzed by Agilent Whole Mouse Genome 4x44 formate oligo arrays (014868) (Agilent Technologies) following the Agilent 1-color microarray-based gene expression analysis protocol.
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