To identify gene expression that distinguishes hematopoietic cells that express PRAME from those that do not, normal CD34+ cells with forced PRAME expression were compared to cells without PRAME expression in culture over time (days 4, 7, 14) using Affymetrix HU-133A microarrays
The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells.
Specimen part, Time
View SamplesA major role of NINJA is to repress root jasmonate signalling and allow normal cell elongation.
Multilayered Organization of Jasmonate Signalling in the Regulation of Root Growth.
Specimen part
View Samplesperipheral blood samples of two leukemia patients in remission were profiled by single cell RNA sequencing approximately 1 year after receiving WT1 specific transgenic T cell therapy, at a time when patients were in clinical remission Overall design: single cell RNA sequencing of peripheral blood mononuclear cells
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Specimen part, Disease, Subject
View SamplesAtaxin 1 (Atxn1) is a protein of unknown function associated with cerebellar neurodegeneration in spinocerebellar ataxia type 1 (SCA1). SCA1 is caused by an expanded polyglutamine within Atxn1 by gain-of-function mechanisms. Lack of Atxn1 in mice triggers motor deficits in the absence of neurodegeneration or apparent neuropathological abnormalities.We extracted RNA from cerebellum of 5 Atxn1-null mice and 5 WT. Cerebellar gene expression profiles at 15 weeks of age were generated usSCA1 ing Affymetrix MOE430A arrays. Identifying the molecular pathways regulated by Atxn1 can provide insights into the early molecular mechanisms underlying neuronal dysfunction.
Down-regulation of the dopamine receptor D2 in mice lacking ataxin 1.
Age, Specimen part
View SamplesWe used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFB3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.
Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.
Specimen part, Time
View SamplesAPE1 was knocked down using siRNA in low passage patient-derived PDAC cells and the resulting cells, along with control cells were analysed using scRNA-seq to identify differentially expressed genes and pathways as a result of APE1 knock-down. Overall design: siRNA APE1 knock-down versus scrambled control, The SMARTer system was used to generate cDNA from 96 captured single cells. Unstranded 2x100bp reads were sequenced using a HiSeq2500 on rapid run mode in 1 lane.
APE1/Ref-1 knockdown in pancreatic ductal adenocarcinoma - characterizing gene expression changes and identifying novel pathways using single-cell RNA sequencing.
Subject
View SamplesComparison of human prepuberal articular and growth plate cartilage
Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis.
Specimen part
View SamplesDespite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. In the present study, we aimed to identify resistance mechanisms to the small-molecule tyrosine kinase inhibitor nintedanib in the Py2T murine breast cancer transplantation model. To identify differences in gene expression between short- and long-term nintedanib and untreaded FAC-sorted tumor and endothelial cells, we performed gene expression profiling by using affymetrix microarrays.
Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy.
Specimen part, Treatment
View SamplesMetastasis 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.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines.
Sex, Specimen part, Disease, Cell line, Treatment
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