The transcriptome analysis of regulatory networks in RA-FLSs
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ABSTRACT:
PROVIDER: PRJNA528936 | ENA |
REPOSITORIES: ENA
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Project description:Rheumatoid arthritis (RA) is a common chronic inflammatory joint disease characterized by persistent synovial hyperplasia and progressive destruction of joint cartilage and bone.Fibroblast-like synoviocytes (FLSs), a prominent component of hyperplastic synovial pannus tissue, are the primary effector cells in RA synovial hyperplasia and invasion. However, the underlying molecular mechanisms remain unclear. Here, we apply transcriptome to assay the regulatory networks which contribute to the proliferation, migration and invasion of RA-FLSs .
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Project description:Co-expression networks and gene regulatory networks (GRNs) are emerging as important tools for predicting the functional roles of individual genes at a system-wide scale. To enable network reconstructions we built a large-scale gene expression atlas comprised of 62,547 mRNAs, 17,862 non-modified proteins, and 6,227 phosphoproteins harboring 31,595 phosphorylation sites quantified across maize development. There was little edge conservation in co-expression and GRNs reconstructed using transcriptome versus proteome data yet networks from either data type were enriched in ontological categories and effective in predicting known regulatory relationships. This integrated gene expression atlas provides a valuable community resource. The networks should facilitate plant biology research and they provide a conceptual framework for future systems biology studies highlighting the importance of studying gene regulation at several levels.
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Project description:Co-expression networks and gene regulatory networks (GRNs) are emerging as important tools for predicting the functional roles of individual genes at a system-wide scale. To enable network reconstructions we built a large-scale gene expression atlas comprised of 62,547 mRNAs, 17,862 non-modified proteins, and 6,227 phosphoproteins harboring 31,595 phosphorylation sites quantified across maize development. There was little edge conservation in co-expression and GRNs reconstructed using transcriptome versus proteome data yet networks from either data type were enriched in ontological categories and effective in predicting known regulatory relationships. This integrated gene expression atlas provides a valuable community resource. The networks should facilitate plant biology research and they provide a conceptual framework for future systems biology studies highlighting the importance of studying gene regulation at several levels.
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Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Several breast cancer cells respond to the antiproliferative effects of RA, but others are RA-resistant. In several cases resistance has been correlated to the amplification of the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene, but the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here we compared two human breast cancer cell lines, the MCF7 cell line, which responds to the antiproliferative action of RA and the BT474 cell line, which is RA-resistant subsequent to ERBB2 amplification in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells. The panel of the RA-regulated genes was also different. Overall our results indicate that ERBB2 amplification interferes with the ability of RA to activate kinases with consequences on the phosphorylation of several proteins involved in transcription and thus on gene expression.
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Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
2016-07-05 | PXD004357 | Pride
Project description:Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome".
2020-10-15 | PXD005911 | Pride
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Project description:To uncover the mechanism that Wnt signaling modulates RA-induced ESC differentiation, we conducted time course RNA-seq analysis during the differentiation. Transcriptome profiles of RA-induced and RA/CHIR-induced ESC differentiation were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000. The RNA-seq data revealed a significant decrease in mesoderm (one of the major source of vascular SMCs) markers and increase in PrE markers in CHIR treated samples, while other lineage markers showed no significant expression, implying a diverging to PrE fate by Wnt activation. Subsequent hierarchical clustering analysis also showed that the gene expression profiles of cells derived from RA induction alone clustered with adult SMCs, while cells derived from RA/CHIR induction gradually clustered to XEN cells with differentiation and was very close to XEN cells at day 16, suggesting that RA/CHIR-induced ESCs differentiated into PrE lineage. This study provided new insights into the importance of RA/Wnt crosstalk in the lineage differentiation of ESCs.
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