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SRP045639
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq2000
Description
An unbalanced karyotype, a condition known as aneuploidy, has a profound impact on cellular physiology and is a hallmark of cancer. Determining how aneuploidy affects cells is thus critical to understanding tumorigenesis. Here we show that aneuploidy interferes with the degradation of autophagosomes within lysosomes. Mis-folded proteins that accumulate in aneuploid cells due to aneuploidy-induced proteomic changes overwhelm the lysosome with cargo, leading to the observed lysosomal degradation defects. Importantly, aneuploid cells respond to lysosomal saturation. They activate a lysosomal stress pathway that specifically increases the expression of genes needed for autophagy-mediated protein degradation. Our results reveal lysosomal saturation as a universal feature of the aneuploid state that must be overcome during tumorigenesis. Overall design: RPE-1 cells either untreated or treated with one of Reversine, Bafilomycin A1 or MG132, each condition was done in triplicate. D14-*_Control: untreated control D14-*_Rev: cells treated with 0.5uM Reversine for 24hrs and harvested 48hrs later D14-*_Baf: cells treated with 0.1uM BafA1 for 6hrs D14-*_Mg: cells treated with 1uM MG132 for 24 hrs
Publication Title
Aneuploidy-induced cellular stresses limit autophagic degradation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Aneuploidy, a state of karyotype imbalance, is a hallmark of cancer. Changes in chromosome copy number have been proposed to drive disease by modulating the dosage of cancer driver genes and by promoting cancer genome evolution. Given the potential of cells with abnormal karyotypes to become cancerous, do pathways exist that limit the prevalence of such cells? By investigating the immediate consequences of aneuploidy on cell physiology, we identified mechanisms that eliminate aneuploid cells. We find that chromosome mis-segregation leads to replication stress, generating further genomic instability, increased karyotype complexity, and ultimately cell cycle arrest. Cells with complex karyotypes exhibit features of senescence and a pro-inflammatory response that promotes their clearance by the immune system. We propose that cells with abnormal karyotypes generate a signal for their own elimination that might well be a source of cancer cell immunosurveillance that must be overcome during malignant transformation. Overall design: Assay the transcriptional impact of aneuploidy by comparing the transcriptomes Euploid control RPE-1 cells in Aneuploid cycling RPE-1 cells and Aneuploid arrested RPE-1 cells using RNA-Seq.
Publication Title
Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1 year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray based approach. Expression of 190 genes was impaired in murine HCC from which 65 were further validated by low-density array RT PCR. The expression of the best 45 genes was then investigated in human samples resulting in 18 genes which expression was significantly modified in HCC. Among them, JUN, methionine adenosyltransferase 1A and 2A, phosphoglucomutase 1, and acyl CoA dehydrogenase short branched chain indicate defective cell proliferation as well as one carbon pathway, glucose and fatty acid metabolism, both in HCC and cirrhotic liver, a well known preneoplastic condition. These alterations were further confirmed in public transcriptomic datasets from other authors. In addition, vasodilator stimulated phosphoprotein, an actin-associated protein involved in cytoskeleton remodelling, was also found to be increased in the liver and serum of cirrhotic and HCC patients. In addition to revealing the impairment of central metabolic pathways for liver homeostasis, further studies may probe the potential value of the reported genes for the early detection of HCC.
Publication Title
A signature of six genes highlights defects on cell growth and specific metabolic pathways in murine and human hepatocellular carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their non-transformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, even these genes are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.
Publication Title
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Bulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
Publication Title
<i>Cis-</i>activation in the Notch signaling pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Specific vulnerability of neurons in the human entorhinal cortex has been associated with the onset of disease.
Publication Title
Differential gene expression analysis of human entorhinal cortex support a possible role of some extracellular matrix proteins in the onset of Alzheimer disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
The aim of this study was to establish an in vitro model to investigate the initial stages of human implantation based on co-culture of a) immortalized cells representing the receptive (Ishikawa) or non-receptive (HEC-1-A) endometrial epithelium with b) spheroids of a trophoblastic cell line (JEG-3) modified to express green fluorescent protein. After co-culturing Ishikawa cells with trophoblast spheroids, 310 and 298 genes increased or decreased their expression compared to non-co-cultured Ishikawa control cells, respectively; only 9 genes (5 increased and 4 decreased) were differentially expressed in HEC-1-A upon co-culture with trophoblast spheroids. Compared to HEC-1-A, the trophoblast challenge to Ishikawa cells differentially regulated the expression of 495 genes. In summary, upon co-culture with the trophoblast spheroids, non-receptive epithelium is characterized by a muted transcriptional response which in turn fails to activate the full transcriptional response that trophoblast spheroids undergo when co-cultured with receptive epithelium. Overall design: GFP expressing JEG-3 spheroids were co-cultured with confluent monolayers of receptive Ishikawa or non-receptive HEC-1-A epithelia. After 48 hours of co-culture, GFP+ (trophoblast JEG-3 spheroid cells) and GFP- cell fractions (receptive Ishikawa or non-receptive HEC-1-A epithelial cells) were isolated by fluorescence-activated flow cytometry (FACS). The specific transcriptional changes of the isolated cell populations were analyzed by RNA-seq profiling. Statistical significance of gene expression differences was set at an absolute log2 fold change (log2FC) =1 and an adjusted p-value <0.05.
Publication Title
Transcriptomic analysis of the interaction of choriocarcinoma spheroids with receptive vs. non-receptive endometrial epithelium cell lines: an in vitro model for human implantation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
The goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples