Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers using a set of specific genes that are regulated by RON/MSP through MBD4-directed aberrant DNA methylation revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent prevents activation of the RON/MBD4 pathway and blocks metastasis of patient-derived breast tumor grafts in vivo. Overall design: Examination of 3 cell types.
The RON receptor tyrosine kinase promotes metastasis by triggering MBD4-dependent DNA methylation reprogramming.
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Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation.
Sex, Specimen part
View SamplesWe report the application of Affymetrix technology for high-throughput profiling of the transcriptome of the rheumatoid arthritis (RA) rat model induced by collagen type II (CIA), with acupuncture, Methotrexate, Isofluorane anesthetic and placebo treatments, as well as the healthy control.
Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation.
Sex, Specimen part
View SamplesWe report the application of Illumina Hiseq2000 sequencing technology for high-throughput miRNA profiling of the rheumatoid arthritis (RA) rat model induced by collagen type II (CIA), with acupuncture and placebo treatments. Overall design: The experiment is designed as 2 arms: epidermal needle manipulation (AP/MEC) and placebo (PLA, used as control) on CIA induced rheumatoid arthritis (RA) rats. Muscle tissue samples sampling was carried out before any therapy in RA rats (RA_T0), and after at 1 hour and 34 days of therapeutic treatments for both AP and PLA. From all the 10 blood collected samples (2 replicates for each group, for each timepoint), total RNA were extracted. Finally, purified RNA were analyzed using illumina hiseq 2000).
Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation.
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View SamplesWe report the application of Affymetrix technology for high-throughput profiling of the transcriptome of the rheumatoid arthritis (RA) rat model induced by collagen type II (CIA), with acupuncture and Methotrexate+acupuncture treatment, as well as epidermal needle manipulation on healthy rat model.
Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation.
Sex, Specimen part
View SamplesBackground In flowering plants, the anther is the site of male gametophyte development. Two major events in the development of the male germline are meiosis and the asymmetric division in the male gametophyte that gives rise to the vegetative and generative cells, and the following mitotic division in the generative cell that produces two sperm cells. Anther transcriptomes have been analyzed at progressive stages of development by using microarray and sequence by synthesis technologies to identify genes that regulate anther development. Here we have carried out a comprehensive analysis of rice anther transcriptomes at four distinct stages of development with a focus to identify regulatory components contributing to male meiosis and germline development. Further, these transcriptomes have been compared with transcriptomes of 10 stages of rice vegetative and seed development to identify genes that express specifically during anther development. Results - To understand the molecular processes that lead to male gametophyte development, transcriptome profiling of four stages of anther development in rice [pre-meiotic (PMA), meiotic (MA), anthers at single-celled (SCP) and tri-nucleate pollen (TPA)] was conducted. Around 22,000 genes were found to be expressed in at least one of the anther developmental stages, with the highest number in MA (18,090) and lowest (15,465) in TPA. Comparison of these transcriptome profiles to an in-house generated microarray-based transcriptomics database comprising of 10 stages/tissues of vegetative as well as reproductive development in rice resulted in the identification of1,000 genes that are specifically expressed in anther stages. Of them the expression of 453 genes was found to be specific to TPA, whereas 78 and 184 genes were expressed specifically in MA and SCP. Gene ontology and pathway analysis of specifically expressed genes revealed that transcription factors and protein folding, sorting and degradation pathway genes dominated in MA, whereas in TPA, those coding for cell structure and signal transduction components were in abundance. Interestingly, about 50% of the genes with anther-specific expression have not been annotated so far. Conclusions - These data not only provide the transcriptome constituents of four landmark stages of anther development but also identify genes that express exclusively in these stages and therefore may contribute to specific aspects of anther and/or male gametophyte development in rice. Moreover, these gene sets assist in building a deeper understanding of underlying regulatory networks and in selecting candidates for gene function validation.
Analysis of anther transcriptomes to identify genes contributing to meiosis and male gametophyte development in rice.
Specimen part
View SamplesWe report the application of Illumina Hiseq2000 sequencing technology for high-throughput profiling of the transcriptome of the rheumatoid arthritis (RA) rat model induced by collagen type II (CIA) and treated with acupuncture or not. Overall design: 2 rats in total, i.e., 2 replicates RA rat model before treatment (RA1, 2) for 3 in vitro culture conditions (standard serum FBS, blood serum from animals acupuncture treated AP+, blood serum from animals acupuncture untreated AP-).
Systemic Wound Healing Associated with local sub-Cutaneous Mechanical Stimulation.
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Gene expression patterns related to osteogenic differentiation of bone marrow-derived mesenchymal stem cells during ex vivo expansion.
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View SamplesThe aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells, including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis.
Gene expression patterns related to osteogenic differentiation of bone marrow-derived mesenchymal stem cells during ex vivo expansion.
No sample metadata fields
View SamplesThe aim of this study was to describe the gene expression patterns related to the differentiation and mineralization of bone-forming cells, including activation and/or repression of osteogenic or non-osteogenic pathways, remodeling of cell architecture, cell adhesion, cell communication, and assembly of extracellular matrix. The study implied patient selection, tissue collection, isolation and culture of human marrow stromal cells (hMSC) and osteoblasts (hOB), and characterization of bone-forming cells. RNA samples were collected at defined time points, in order to understand the regulation of gene expression during the processes of cell differentiation/mineralization that occur during bone repair. Transcriptome analysis was performed by using the Affymetrix GeneChip microarray technology platform and GeneChip Human Genome U133 Plus 2.0 Array. Our results help to design a gene expression profile of bone-forming cells during specific steps of osteogenic differentiation. These findings offer an useful tool to monitor the behaviour of osteogenic precursors cultured in presence of exogenous stimuli, i.e. growth factors, or onto 3D scaffolds for bone engineering. Moreover, they can contribute to identify and clarify the role of new genes for a better understanding of the molecular mechanisms regulating osteogenesis.
Gene expression patterns related to osteogenic differentiation of bone marrow-derived mesenchymal stem cells during ex vivo expansion.
No sample metadata fields
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