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GSE18027
Homo sapiens
8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
RNAi mediated knockdown of BTG1 in the acute lymphoblastic cell line RS4;11 causes this cell line to become resistant to prednisolone treatment when compared to control cells.
Publication Title
BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification and evaluation of specific molecular markers is of great importance for reliable diagnostics and outcome prediction of renal neoplasms
Publication Title
High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 298 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version, custom CDF (huex10st)
Description
Four different molecular classifications of muscle-invasive bladder cancer (MIBC) based on gene expression have been proposed. With the ultimate goal of utilizing these molecular subtypes for personalized treatment, we investigated their significance in the context of neoadjuvant cisplatin-based chemotherapy (NAC).
Publication Title
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.
Sample Metadata Fields
Age, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
We sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Overall design: Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples
Publication Title
Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of Parkinsons disease (PD). To identify molecular mechanisms underlying neuronal dysfunction and alpha--synuclein pathology in the premotor phase of PD, we investigated the transcriptome of post-mortem substantia nigra (SN) of iLBD, PD donors and age-matched controls with Braak alpha--synuclein stage ranging from 0-6. In Braak alpha--synuclein stages 1 and 2, we observed deregulation of pathways linked to axonal degeneration, unfolded protein response (UPR), immune response and endocytosis, including axonal guidance signaling, protein kinase A signaling, mTOR signaling, EIF2 signaling and clathrin-mediated endocytosis. In Braak stages 3 and 4, we observed a deregulation in pathways involved in protein translation and cell survival, including mTOR and EIF2 signaling. In Braak stages 5 and 6, we observed deregulation of pathways such as dopaminergic signaling, axonal guidance signaling and thrombin signaling. Throughout the progression of PD pathology, we observed a deregulation of mTOR, EIF2 and regulation of eIF4 and p70S6K signaling in the SN. This implicates that molecular mechanisms related to UPR, axonal dysfunction, endocytosis and immune response are an early event in PD pathology, and may hold the key to altering the disease progression in PD.
Publication Title
Evidence for Immune Response, Axonal Dysfunction and Reduced Endocytosis in the Substantia Nigra in Early Stage Parkinson's Disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is a malignancy of mature, skin-homing T cells. Szary syndrome (Sz) is often considered to represent a leukemic phase of MF. In this study the pattern of numerical chromosomal alterations in MF tumor samples was defined using array-based CGH; simultaneously gene expression was analyzed using microarrays. Highly recurrent chromosomal alterations in MF include copy number gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. This pattern characteristic of MF differs markedly from chromosomal alterations observed in Sz. Integration of data from array-based CGH and gene expression analysis yielded several candidate genes with potential relevance in the pathogenesis of MF. We confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain, demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes showed diminished expression associated with loss. In addition, it was found that presence of chromosomal alterations on 9p21, 8q24 and 1q21-1q22 was associated with poor prognosis in patients with MF. This study provides novel insight into genetic alterations underlying MF. Furthermore, our analysis uncovered genomic differences between MF and Sz, which suggest that the molecular pathogenesis and therefore therapeutic requirements of these CTCLs may be distinct.
Publication Title
Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2500
Description
In this study we studied the presence of tumor cells that underwent epithelial-to-mesenchymal transition within polyoma middle T antigen (PyMT) breast tumors. For this we dissociated tumors and isolated Ecad positive tumor cells by FACS sorting. We confirmed that PyMT tumors contain a small set of tumor cells that have undergone EMT in the primary tumor and that E-cadherin can be used as a marker on single cell level for mesenchymal status in this model. Overall design: (i) We isolated primary tumors from mice, dissociated the tumors and FACS-sorted for single Ecad positive tumor cells, after this we performed single cell sequencing of the cells. (ii) We isolated CTCs and solid tumor cells from mice, dissociated the tumors and FACS-sorted for single Ecad positive and negative cells, after this we performed single cell sequencing of the cells.
Publication Title
Plasticity between Epithelial and Mesenchymal States Unlinks EMT from Metastasis-Enhancing Stem Cell Capacity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 166 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T-cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. In this study, we performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN- to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlation between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.
Publication Title
Integrated Whole Genome and Transcriptome Analysis Identified a Therapeutic Minor Histocompatibility Antigen in a Splice Variant of ITGB2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 34 Downloadable Samples
- IlluminaHiSeq2500, NextSeq500
Description
Understanding the development and function of an organ requires the characterization of all of its cell types. Traditional methods for visualizing and isolating sub-populations of cells are based on mRNA or protein expression of only few known marker genes. The unequivocal identification of a specific marker gene, however, poses a major challenge, particularly if this cell type is rare. Identifying rare cell types, such as stem cells, short-lived progenitors, cancer stem cells, or circulating tumor cells is crucial to acquire a better understanding of normal or diseased tissue biology. To address this challenge we sequenced the transcriptome of hundreds of randomly selected cells from mouse intestinal organoids, cultured self-organizing epithelial structures that contain all cell lineages of the mammalian intestine. Organoid buds, like intestinal crypts, harbor stem cells that continuously differentiate into a variety of cell types, occurring at widely different abundances. Since available computational methods can only resolve more abundant cell types, we developed RaceID, an algorithm for rare cell type identification in complex populations of single cells. We demonstrate that this algorithm can resolve cell types represented by only a single cell in a population of randomly sampled organoid cells. We use this algorithm to identify Reg4 as a novel marker for enteroendocrine cells, a rare population of hormone producing intestinal cells. Next, we use Reg4 expression to enrich for these rare cells and investigate the heterogeneity within this population. Reassuringly, RaceID confirmed the existence of known enteroendocrine lineages, and moreover, discovered novel subtypes, which we subsequently validated in vivo. Having validated RaceID by this proof-of-principle experiment we then apply the algorithm to ex vivo isolated LGR5 positive cells and their direct progeny and demonstrate homogeneity of the stem cell pool. We envision broad applicability of our method for discovering rare cell types and the corresponding marker genes in healthy and diseased organs. Overall design: Small intestinal crypts were isolated from a single wild-type C57BL/6 mouse, a Reg4-dsRed-knock-in mouse and an Lgr5-GFP-DTR mouse. The crypts were propagated and expanded in culture as organoids. For each experiment, multiple organoids were harvested and dissociated into single cells. Each experiment was done twice, using different passage of the same organoid culture. We also included a pool-and-split control for 96 Reg4-dsRed positive intetsinal cells and a control library with 5 mouse embryonic stem cells (wells 1-5), 5 mouse embryonic fibroblasts (wells 6-10), 75 random organoid cells (wells 11-85), 5 wells without primer and without template (wells 86 and 93-96), and five wells with primer and without template (wells 87-92). We also sequenced two 96 well plates of Lgr5-EGFP positive single cells isolated ex vivo, and Lgr5 progeny collected after five days of lineage tracing. Label induction was performed using an Lgr5-Cre reporter mouse expressing YFP from Rosa26 promoter with a loxP flanked transcriptional road block in between. Five 96 well plates of YFP positive were sequenced. Sample number four also contains also unrelated samples (single cell barcode 49-96), which should be discarded.
Publication Title
Single-cell messenger RNA sequencing reveals rare intestinal cell types.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Kupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. CONCLUSION: Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity.
Publication Title
Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity.
Sample Metadata Fields
Sex
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